研究者詳細 - 長谷川　奉延

論文 - 長谷川　奉延

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DHX37 Variant Is One of the Common Genetic Causes in Japanese Patients with Testicular Regression Syndrome/Partial Gonadal Dysgenesis without Müllerian Derivatives

Shimura K., Ichihashi Y., Nakano S., Sato T., Hamajima T., Numasawa K., Narumi S., Hasegawa T., Ishii T.

Hormone Research in Paediatrics 98 （ 2 ） 206 - 213 2025年04月

ISSN 16632818

Introduction: The testicular regression syndrome (TRS) is a form of differences of sex development (DSD) in which the testes differentiate and function during early embryonic development, but subsequently regress. The clinical phenotype of TRS often overlaps with that of partial gonadal dysgenesis (PGD). Previous studies have demonstrated a causal association between TRS/ PGD and heterozygous missense variants of DHX37. Methods: We enrolled 11 Japanese 46,XY individuals (from 10 families) with TRS/PGD who exhibited undetected or hypoplastic testes, Müllerian duct regression, and low serum testosterone or anti- Müllerian hormone levels. The subjects underwent targeted sequencing of 36 known causative genes for DSD, PCR-based Sanger sequencing of DHX37, or whole-exome sequencing. Results: Previously described pathogenic variants or novel nonsense variants (SRY, NR5A1, and DMRT1) were observed in four out of 10 families. Additionally, we identified two heterozygous rare variants of DHX37 in four families: a previously reported pathogenic variant (c.923G>A, p.Arg308Gln) in three and a novel likely pathogenic variant (c.1882A>C, p.Thr628Pro) in one. The external genitalia of patients with the DHX37 variants varied from female-type to male-type without micropenis. Eighty percent of Japanese patients with TRS/PGD had monogenic disorders including DHX37 variant being the most commonly identified (40%). The external or internal genital phenotype of TRS/PGD overlaps between DHX37 variant carriers and others. Conclusions: DHX37 variant is one of the common genetic causes in Japanese patients with TRS/PGD without Müllerian derivatives. Genetic test is helpful in detecting DHX37- related TRS/PGD because of the phenotypic diversity of the external genitalia in this disorder.

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Reference Values of Arm Span and Arm Span to Height Ratio of Japanese Population in Childhood and Adolescence: Comparison With Dutch and Turkish Population

Hirano Y., Inokuchi M., Narumi S., Hasegawa T.

American Journal of Human Biology 37 （ 4 ） 2025年04月

ISSN 10420533

Objectives: To establish age-specific reference values for the arm span and arm span/height ratio of the Japanese population in children and adolescence and elucidate their characteristics compared with those of other populations. Study Design: We analyzed data from a national survey on the body sizes of Japanese people conducted between 1992 and 1994 by the Research Institute of Human Engineering for Quality Life. This study was an observational cross-sectional study, including 6089 boys and 4970 girls aged between 5.5 and 18.5 years. We constructed the reference values and delineated the reference curves for the arm span and arm span/height ratio of the Japanese population in childhood and adolescence using the LMS method. The references were compared with those of the Dutch and Turkish populations using the reference curve of 0 standard deviation. Results: The arm span of the Japanese population increased throughout childhood, with a particularly large increase at the age of puberty. The arm span/height ratio also increased slowly throughout childhood. The Japanese population had a smaller arm span/height ratio than the Dutch and Turkish populations of all ages in childhood and adolescence. Moreover, the arm span/height ratio of the Japanese population reached a constant value at an earlier age than in the Dutch and Turkish populations. Conclusions: We constructed the first reference values for the arm span of Japanese children and adolescents. The Japanese population has shorter arm lengths in relation to their height, and their arm span/height ratio reaches a constant value at an earlier age, compared with the Dutch and Turkish populations.

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Sex education to an adolescent male with Down syndrome in a single-mother family in Japan

Saito A., Sato T., Shima H., Yamagishi H., Narumi S., Ishii T., Hasegawa T.

Pediatrics International 67 （ 1 ） 2025年01月

ISSN 13288067

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ACVRL1 and MTHFR double variants in an adolescent with paradoxical cerebral embolism

Sato T., Ichihashi Y., Tsuruta H., Chu P.S., Akiyama T., Hishida T., Hasegawa T.

Pediatrics International 67 （ 1 ） 2025年01月

ISSN 13288067

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Recovery from Atrophic Autoimmune Thyroiditis in a Child: Thyroid Stimulation-Blocking Antibody as a Prognostic Marker

Kusano C., Hori N., Hasegawa T., Narumi S.

Hormone Research in Paediatrics 2025年

ISSN 16632818

Introduction: Atrophic autoimmune thyroiditis (AAT) is a form of autoimmune hypothyroidism characterized by the absence of a goiter. Thyroid stimulation-blocking antibody (TSBAb) has been detected in a subset of pediatric AAT cases. Although the disappearance of TSBAb has been related with the recovery of thyroid function in adult AAT cases, similar outcomes have not been documented in pediatric cases. Case Presentation: A 2-year-old Japanese boy presented for evaluation of stunted growth from1 year 10 months of age. Tests for congenital hypothyroidism were negative on newborn screening, and he had no significant medical history. However, he showed symptoms of hypothyroidism (inactiveness, hair loss, dry skin), and primary hypothyroidism was confirmed by blood test (serum TSH level, 818 mU/L; serum free T4 level, <0.40 ng/ dL). The patient exhibited a unique antibody profile: positive for TSH receptor antibody (TRAb) and TSBAb and negative for anti-thyroglobulin antibody (TgAb) and antiperoxidase antibody (TPOAb). He was treated with levothyroxine, after which his growth was normalized. During the 8-year follow-up, the patient's TSBAb levels decreased, allowing for the discontinuation of levothyroxine therapy. Conclusion: We reported the case of a 2-year-old boy diagnosed with AAT who presented with a characteristic antibody profile, negative for TgAb and TPOAb, but positive for TRAb and TSBAb. During 8 years of follow-up, TSBAb seroconversion to negative was observed, leading to treatment discontinuation at age 10 years. This case suggests that monitoring of TSBAb after a diagnosis of AAT may be used to determine treatment discontinuation even in children.

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Familial Non-Autoimmune Hyperthyroidism Caused by an Extracellular Domain Variant (p.Leu267Phe) of the TSH Receptor

Shimura K., Ichihashi Y., Abe K., Ishii T., Hasegawa T., Narumi S.

Hormone Research in Paediatrics 2025年

ISSN 16632818

Introduction: Non-autoimmune hyperthyroidism (NAH) is a rare genetic disorder caused by germline-activating variants in the TSH receptor (TSHR) gene. While most NAH-related TSHR variants are located in the seven-transmembrane domain (7TMD), three variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) have been identified in the extracellular domain (ECD), with p.Leu267Phe previously not showing constitutively active in vitro. Methods: We searched for TSHR variants in a Japanese family with NAH using PCR-based direct sequencing. We created three ECD variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) and a series of variants in which Leu267 was mutated to 18 amino acids other than Leu and Phe. Based on the cryo-electron microscopic structures, we evaluated the structure-function relationship of TSHR. We compared their cAMP-producing capacities to WT-TSHR in the luciferase activity assay using HEK293 cells. Western blot and fluorescence immunostaining were performed using HA-tagged TSHR vectors to compare Leu267Phe-TSHR with WT-TSHR. Results: A heterozygous TSHR variant (p.Leu267Phe) was identified. Comparison of the cryo-electron microscopy structures of the activated and inactivated TSHRs revealed a significant change in the ECD structure around Leu267. The ligand-independent cAMP-producing capacities compared to WT-TSHR were 238 ± 20% (mean ± SEM) for Leu267Phe. Of all 19 possible variants created through systematic mutagenesis, only Leu267Phe-TSHR and Leu267Tyr-TSHR exhibited significantly higher ligand-independent cAMP-producing capacities. Immunoblotting and fluorescence immunostaining showed that the Leu267Phe variant did not affect protein expression levels and intracellular localization of TSHR. Discussion/Conclusion: Leu267Phe-TSHR causes NAH. Substituting Leu267 to aromatic amino acids may shift the equilibrium of the TSHR state toward activation.

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Imaging findings of thyroid diseases in children

Tsujioka Y., Yamada Y., Hasegawa T., Hashimoto M., Jinzaki M.

Clinical Pediatric Endocrinology 34 （ 2 ） 89 - 104 2025年

ISSN 09185739

We review the imaging findings in pediatric thyroid diseases that necessitate prompt diagnosis and timely medical intervention. Congenital hypothyroidism particularly represents a critical pediatric emergency. Ultrasonography stands as the primary modality for accurately assessing thyroid morphology and identifying thyroid dysgenesis.123I-scintigraphy mirrors iodine metabolism and thyroid hormone synthesis, and the concurrent application of perchlorate (perchloride discharge test) elucidates the pathogenesis of thyroid dyshormonogenesis. Nonetheless, radioiodine scintigraphy has seen limited utilization due to the intricacies of pre-test preparation.99mTc-pertechnetate scintigraphy demonstrates high sensitivity in delineating thyroid tissues with minimal radiation exposure, facilitating the diagnosis of thyroid dysgenesis. Additionally, we have included brief insights on the imaging characteristics of central hypothyroidism, thyroiditis, and thyroid masses.

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A Case of Penttinen Syndrome With Radiographic Acroosteolysis From Age 3 Years

Shimura K., Toki M., Tsujioka Y., Nishimura G., Ishii T., Hasegawa T.

American Journal of Medical Genetics, Part A 2025年

ISSN 15524825

Premature aging syndrome, Penttinen type (Penttinen syndrome) is a progeroid syndrome with facial alterations (thin hair and progressive recession of the maxillozygomatic bones with pseudoprognathism), skin abnormalities (scleroderma with epidermal and dermal atrophy, lipoatrophy, chronic ulcers, and keloid-like hypertrophic lesions), corneal changes (vascularization and opacity), cerebral vascular anomalies, and acroosteolysis. This syndrome is caused by heterozygous, gain-of-function pathogenic variants in the PDGFRB gene. Only 10 affected individuals have been reported to date, and thus the phenotypic spectrum of the disorder, particularly in early childhood, remains elusive. We reported here the clinical course of an affected male from early childhood to young adulthood. Thin limbs and short fingers attracted medical attention at age 3 years, at which time he had already developed maxillary hypoplasia, keloids, and acroosteolysis, all of which progressively worsened with age. Joint contractures and scoliosis became apparent during adolescence. Progressive maxillary recession and scleroderma remarkably altered his facial gestalt over time, including the development of exophthalmos, small auricles, short philtrum, and small mouth. Sanger sequencing identified a recurrent, de novo pathogenic variant in the PDGFRB gene (c.1994T > C, p.Val665Ala). This report on the clinical course through childhood provides additional insight into the natural history of Penttinen syndrome.

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Znrf3 exon 2 deletion mice do not recapitulate congenital adrenal hypoplasia

Uchida N., Ishii T., Amano N., Takada S., Kobayashi K., Murakami T., Narumi S., Hasegawa T.

Journal of Molecular Endocrinology 73 （ 4 ） 2024年11月

ISSN 09525041

Wnt/β-catenin signaling is essential for adrenocortical development. Zinc and ring finger 3 (ZNRF3), an E3 ubiquitin ligase that attenuates Wnt/β-catenin signaling, is negatively regulated by R-spondin via an extracellular domain that is partially encoded by exon 2 of ZNRF3. We recently identified ZNRF3 exon 2 deletions in three individuals with congenital adrenal hypoplasia. ZNRF3 exon 2 deletion impairs R-spondin binding, thereby attenuating β-catenin expression and eventually leading to the development of congenital adrenal hypoplasia. To elucidate the influence of ZNRF3/Znrf3 exon 2 deletion on adrenocortical development, we generated homozygous Znrf3 exon 2 deletion (Znrf3Δ2/Δ2) mice. Whereas the adrenal glands of Znrf3Δ2/Δ2 mice did not show gross morphological changes at birth, moderate hyperplasia of the zona fasciculata (ZF), dispersed medulla arrangement, and a radially spreading zone with macrophage infiltration between the ZF and medulla were observed at 6 weeks of age. 20α-hydroxysteroid dehydrogenase, a marker of the adrenal X-zone, was hardly detected by immunostaining, and gene expression was significantly downregulated. The number of activated β-catenin-positive cells decreased in the zona glomerulosa, consistent with the results of in situ hybridization for Axin2, a Wnt/β-catenin target gene. Plasma ACTH and serum corticosterone levels in Znrf3Δ2/Δ2 mice did not differ significantly from those in wild-type mice. These results show a species-specific difference in the effects of ZNRF3/Znrf3 exon 2 deletions in humans and mice; Znrf3Δ2/Δ2 mice do not develop congenital adrenal hypoplasia but instead exhibit moderate ZF hyperplasia, dispersed medulla arrangement, X-zone dysplasia, and macrophage infiltration occurred in the inner cortex.

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Establishment of Star-edited Y1 cells as a novel in vitro functional assay for STAR

Sato T., Narumi S., Sakuma T., Shimura K., Ichihashi Y., Yamamoto T., Ishii T., Hasegawa T.

Journal of Molecular Endocrinology 73 （ 4 ） 2024年11月

ISSN 09525041

Genetic variants involving steroidogenic acute regulatory protein cause lipoid congenital adrenal hyperplasia, which is characterized by impaired steroidogenesis in the adrenal glands and gonads. Functional assessment of variant STAR proteins is necessary for an accurate genetic diagnosis. Ideally, steroidogenic cells should be used to assess the functionality of STAR proteins, but the presence of endogenous STARs in steroidogenic cells precludes such a method. Here, we generated Star-edited cells from steroidogenic Y1 mouse adrenocortical tumor cells by genome editing. Star-edited Y1 cells exhibited very low but measurable cAMP-dependent pregnenolone production. Furthermore, stimulation of the cAMP pathway for 2 weeks resulted in the formation of lipid droplets in the cytoplasm of Star-edited Y1 cells, which resembled the histology of the adrenal glands of patients with lipoid congenital adrenal hyperplasia. The steroidogenic defect of Star-edited Y1 cells can be restored by transient overexpression of mouse Star. We found that human STAR can also restore defective steroidogenesis in Star-edited Y1 cells, and we were able to construct a novel in vitro system to evaluate human STAR variants. Collectively, we established Star-edited Y1 cells that retain the steroidogenic pathway downstream of the Star protein. Star-edited Y1 cells recapitulate the functional and morphological changes of lipoid congenital adrenal hyperplasia and can be used to evaluate the functionality of human STAR variants.

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A Pitfall of Adrenal Hypoplasia Congenita

Abe J., Tsubaki J., Shimura K., Hasegawa T.

Clinical Pediatrics 63 （ 9 ） 1318 - 1320 2024年10月

ISSN 00099228

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Genotype–Phenotype Correlations in 30 Japanese Patients With Congenital Hypothyroidism Attributable to TG Defects

Tanase-Nakao K., Iwahashi-Odano M., Sugisawa C., Abe K., Muroya K., Yamamoto Y., Kawada Y., Mushimoto Y., Ohkubo K., Kinjo S., Shimura K., Aoyama K., Mizuno H., Hotsubo T., Takahashi C., Isojima T., Kina Y., Takakuwa S., Hamada J., Sawaki M., Shigehara K., Sugimoto S., Etani Y., Narumi-Wakayama H., Mine Y., Hasegawa T., Hishinuma A., Narumi S.

Journal of Clinical Endocrinology and Metabolism 109 （ 9 ） 2358 - 2365 2024年09月

ISSN 0021972X

Context: Thyroglobulin (Tg), encoded by TG, is essential for thyroid hormone synthesis. TG defects result in congenital hypothyroidism (CH). Most reported patients were born before the introduction of newborn screening (NBS). Objective: We aimed to clarify the phenotypic features of patients with TG defects diagnosed and treated since the neonatal period. Methods: We screened 1061 patients with CH for 13 CH-related genes and identified 30 patients with TG defects. One patient was diagnosed due to hypothyroidism-related symptoms and the rest were diagnosed via NBS. Patients were divided into 2 groups according to their genotypes, and clinical characteristics were compared. We evaluated the functionality of the 7 missense variants using HEK293 cells. Results: Twenty-seven rare TG variants were detected, including 15 nonsense, 3 frameshift, 2 splice-site, and 7 missense variants. Patients were divided into 2 groups: 13 patients with biallelic truncating variants and 17 patients with monoallelic/biallelic missense variants. Patients with missense variants were more likely to develop thyroid enlargement with thyrotropin stimulation than patients with biallelic truncating variants. Patients with biallelic truncating variants invariably required full hormone replacement, whereas patients with missense variants required variable doses of levothyroxine. Loss of function of the 7 missense variants was confirmed in vitro. Conclusion: To our knowledge, this is the largest investigation on the clinical presentation of TG defects diagnosed in the neonatal period. Patients with missense variants showed relatively mild hypothyroidism with compensative goiter. Patients with only truncating variants showed minimal or no compensative goiter and required full hormone replacement.

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Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study

Hosokawa M., Ichihashi Y., Sato Y., Shibata N., Nagasaki K., Ikegawa K., Hasegawa Y., Hamajima T., Nagamatsu F., Suzuki S., Numakura C., Amano N., Sasaki G., Nagahara K., Soneda S., Ariyasu D., Maeda M., Kamasaki H., Aso K., Hasegawa T., Ishii T.

Journal of Clinical Endocrinology and Metabolism 109 （ 8 ） e1602 - e1607 2024年08月

ISSN 0021972X

Context: Adrenal crisis (AC) is a life-threatening complication that occurs during follow-up of patients with adrenal insufficiency (AI). No prospective study has thoroughly investigated AC in children with primary and secondary AI. Objective: This work aimed to determine the incidence and risk factors for AC in patients with pediatric-onset AI. Methods: This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at age ≤15 years. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis. Results: The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% CI, 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93; 95% CI, 0.89-0.97) and increased number of infections (RR 1.17; 95% CI, 1.07-1.27) as significant risk factors. Female sex (RR 0.99; 95% CI, 0.53-1.86), primary AI (RR 0.65; 95% CI, 0.30-1.41), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02; 95% CI, 0.96-1.08) was not a significant risk factor. Conclusion: A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients.

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Uchida N., Ishii T., Nishimura G., Sato T., Kuratsuji G., Nagasaki K., Hosokawa Y., Adachi E., Takasawa K., Kashimada K., Tsujioka Y., Hasegawa T.

American Journal of Medical Genetics, Part A 194 （ 6 ） 2024年06月

ISSN 15524825

Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G. Based on the manifestations in the Finnish and Amish individuals, the hallmarks of CHH are prenatal-onset growth failure, metaphyseal dysplasia, hair hypoplasia, immunodeficiency, and other extraskeletal manifestations. Herein, we report six Japanese individuals with CHH from four families. All probands presented with moderate short stature with mild metaphyseal dysplasia or brachydactyly. One of them had hair hypoplasia and the other immunodeficiency. By contrast, the affected siblings of two families showed only mild short stature. We also reviewed all previously reported 13 Japanese individuals. No n.71A > G allele was detected. The proportions of Japanese versus Finnish individuals were 0% versus 70% for birth length < −2.0 SD, 84% versus 100% for metaphyseal dysplasia and 26% versus 88% for hair hypoplasia. Milder manifestations in the Japanese individuals may be related to the difference of genotypes. The mildest form of CHH phenotypes is mild short stature without overt skeletal alteration or extraskeletal manifestation and can be termed “RMRP-related short stature”.

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Functional variants in a TTTG microsatellite on 15q26.1 cause familial nonautoimmune thyroid abnormalities

Narumi S., Nagasaki K., Kiriya M., Uehara E., Akiba K., Tanase-Nakao K., Shimura K., Abe K., Sugisawa C., Ishii T., Miyako K., Hasegawa Y., Maruo Y., Muroya K., Watanabe N., Nishihara E., Ito Y., Kogai T., Kameyama K., Nakabayashi K., Hata K., Fukami M., Shima H., Kikuchi A., Takayama J., Tamiya G., Hasegawa T.

Nature Genetics 56 （ 5 ） 869 - 876 2024年05月

ISSN 10614036

Insufficient thyroid hormone production in newborns is referred to as congenital hypothyroidism. Multinodular goiter (MNG), characterized by an enlarged thyroid gland with multiple nodules, is usually seen in adults and is recognized as a separate disorder from congenital hypothyroidism. Here we performed a linkage analysis of a family with both nongoitrous congenital hypothyroidism and MNG and identified a signal at 15q26.1. Follow-up analyses with whole-genome sequencing and genetic screening in congenital hypothyroidism and MNG cohorts showed that changes in a noncoding TTTG microsatellite on 15q26.1 were frequently observed in congenital hypothyroidism (137 in 989) and MNG (3 in 33) compared with controls (3 in 38,722). Characterization of the noncoding variants with epigenomic data and in vitro experiments suggested that the microsatellite is located in a thyroid-specific transcriptional repressor, and its activity is disrupted by the variants. Collectively, we presented genetic evidence linking nongoitrous congenital hypothyroidism and MNG, providing unique insights into thyroid abnormalities.

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Letter to the Editor regarding “Serum steroid metabolite profiling by LC-MS/MS in two phenotypic male patients with HSD17B3 deficiency: Implications for hormonal diagnosis”

Sato T., Nakano S., Honda M., Narumi S., Ishii T., Hasegawa T.

Journal of Steroid Biochemistry and Molecular Biology 239 2024年05月

ISSN 09600760

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A MinION-based Long-Read Sequencing Application With One-Step PCR for the Genetic Diagnosis of 21-Hydroxylase Deficiency

Adachi E., Nakagawa R., Tsuji-Hosokawa A., Gau M., Kirino S., Yogi A., Nakatani H., Takasawa K., Yamaguchi T., Kosho T., Murakami M., Tajima T., Hasegawa T., Yamada T., Morio T., Ohara O., Kashimada K.

Journal of Clinical Endocrinology and Metabolism 109 （ 3 ） 750 - 760 2024年03月

ISSN 0021972X

Context: Recently developed long-read sequencing (LRS) technology has been considered an option for CYP21A2 analysis. However, the clinical use of LRS for CYP21A2 analysis is limited. Objective: This study’s objective is to develop an efficient and low-cost LRS system for CYP21A2 screening. Methods: A DNA fragment library was prepared in a single polymerase chain reaction (PCR) that covers the entire CYP21A2 gene and all known junctions caused by TNXB gene structural rearrangements, yielding a single 8-kb product of CYP21A2 or CYP21A1P/CYP21A2 chimera. After barcoding, the PCR products were sequenced on a MinION-based platform with Flongle Flow Cell R9.4.1 and R10.4.1. Results: The reference genotypes of 55 patients with 21-hydroxylase deficiency (21OHD) were established using the conventional method with multiplex ligation-dependent probe amplification (MLPA) and nested PCR. LRS using Flongle Flow Cell R9.4.1 yielded consistent results. Additionally, the recently updated LRS “duplex” analysis with Flongle flow cell R10.4.1 was tested to reveal an advantage of accurately sequencing a variant located on the homopolymer region. By introducing a barcode system, the cost was reduced to be comparable to that of conventional analysis. A novel single-nucleotide variation was discovered at the acceptor site of intron 7, c.940-1G > C. We also identified a subtype of the classical chimeric junction CH2, “CH2a,” in the region from the latter part of intron 5 to exon 6. Conclusion: We successfully established a novel low-cost and highly accurate LRS system for 21OHD genetic analysis. Our study provides insight into the feasibility of LRS for diagnosing 21OHD and other genetic diseases caused by structural rearrangements.

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Single-Exon Deletions of ZNRF3 Exon 2 Cause Congenital Adrenal Hypoplasia

Amano N., Narumi S., Aizu K., Miyazawa M., Okamura K., Ohashi H., Katsumata N., Ishii T., Hasegawa T.

Journal of Clinical Endocrinology and Metabolism 109 （ 3 ） 641 - 648 2024年03月

ISSN 0021972X

Context: Primary adrenal insufficiency (PAI) is a life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient steroid hormones. E3 ubiquitin protein ligase zinc and ring finger 3 (ZNRF3) is a negative regulator of Wnt/β-catenin signaling. R-spondin 1 (RSPO1) enhances Wnt/β-catenin signaling via binding and removal of ZNRF3 from the cell surface. Objective: This work aimed to explore a novel genetic form of PAI. Methods: We analyzed 9 patients with childhood-onset PAI of biochemically and genetically unknown etiology using array comparative genomic hybridization. To examine the functionality of the identified single-exon deletions of ZNRF3 exon 2, we performed three-dimensional (3D) structure modeling and in vitro functional studies. Results: We identified various-sized single-exon deletions encompassing ZNRF3 exon 2 in 3 patients who showed neonatal-onset adrenal hypoplasia with glucocorticoid and mineralocorticoid deficiencies. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the 3 distinct single-exon deletions were commonly transcribed into a 126-nucleotide deleted mRNA and translated into 42-amino acid deleted protein (ΔEx2-ZNRF3). Based on 3D structure modeling, we predicted that interaction between ZNRF3 and RSPO1 would be disturbed in ΔEx2-ZNRF3, suggesting loss of RSPO1-dependent activation of Wnt/β-catenin signaling. Cell-based functional assays with the TCF-LEF reporter showed that RSPO1-dependent activation of Wnt/β-catenin signaling was attenuated in cells expressing ΔEx2-ZNRF3 as compared with those expressing wild-type ZNRF3. Conclusion: We provided genetic evidence linking deletions encompassing ZNRF3 exon 2 and congenital adrenal hypoplasia, which might be related to constitutive inactivation of Wnt/β-catenin signaling by ΔEx2-ZNRF3.

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Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression

Takahashi F., Baba T., Christianto A., Yanai S., Lee-Okada H.C., Ishiwata K., Nakabayashi K., Hata K., Ishii T., Hasegawa T., Yokomizo T., Choi M.H., Morohashi K.i.

Cell Reports 43 （ 2 ） 2024年02月

The zona fasciculata (zF) in the adrenal cortex contributes to multiple physiological actions through glucocorticoid synthesis. The size, proliferation, and glucocorticoid synthesis characteristics are all female biased, and sexual dimorphism is established by androgen. In this study, transcriptomes were obtained to unveil the sex differentiation mechanism. Interestingly, both the amount of mRNA and the expressions of nearly all genes were higher in females. The expression of Nr5a1, which is essential for steroidogenic cell differentiation, was also female biased. Whole-genome studies demonstrated that NR5A1 regulates nearly all gene expression directly or indirectly. This suggests that androgen-induced global gene suppression is potentially mediated by NR5A1. Using Nr5a1 heterozygous mice, whose adrenal cortex is smaller than the wild type, we demonstrated that the size of skeletal muscles is possibly regulated by glucocorticoid synthesized by zF. Taken together, considering the ubiquitous presence of glucocorticoid receptors, our findings provide a pathway for sex differentiation through glucocorticoid synthesis.

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Usefulness of a mobile airwayscope with a monitor in examination of the external genitalia of a 483 g female neonate

Hiraizumi T., Sato T., Kobayashi H., Arimitsu T., Narumi S., Ishii T., Hasegawa T.

Pediatrics International 66 （ 1 ） 2024年01月

ISSN 13288067

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Siblings of neonatal hyperbilirubinemia with UGT1A1 double missense variants

Kubota Y., Sato T., Matsuyama M., Maruo Y., Narumi S., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 33 （ 3 ） 195 - 198 2024年

ISSN 09185739

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Underweight in young Japanese women over time: a longitudinal retrospective study of the change in body mass index from ages 6 to 20 years

Nagashima Y., Inokuchi M., Sato Y., Hasegawa T.

Annals of Human Biology 51 （ 1 ） 2024年

ISSN 03014460

Background: The high prevalence of underweight in young women has become a serious health problem in Japan. When and how young women reach a low body mass index (BMI) has not been clarified. Aim: To clarify the characteristics of BMI standard deviation scores (BMI SDS) trajectory of young Japanese women with underweight. Subjects and methods: A total of 601 Japanese female university students aged 20 years were classified into underweight and healthy weight groups. Their school health check-up data were available from the ages of 6 to 20 years. We evaluated the estimated mean values of BMI SDS at each age and differences in BMI SDS (ΔBMI SDS) from 6 years to each age using a mixed-effects model and compared between the two groups at each age. Results: In the underweight group, the BMI SDS at every age (−1.67 to −0.91) and the ΔBMI SDS after 16 years of age (−0.76 to −0.38) were significantly lower than those in the healthy weight group (−0.41 to −0.13, −0.07 to 0.04), respectively. Conclusion: Young Japanese women with underweight have at least two characteristics of BMI SDS trajectory: being constitutionally underweight and shifting their weight status from baseline towards underweight in their late teens.

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Adrenal crisis during a trip in a young child with septo-optic dysplasia

Takahashi M., Sato T., Nakano S., Hamada J., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 33 （ 2 ） 101 - 103 2024年

ISSN 09185739

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Pitfalls in estradiol measurement by electrochemiluminescence immunoassay: A case study of a prepubertal girl with a falsely elevated serum estradiol level

Furusawa K., Hachiya R., Shibata H., Uchida N., Sasaki G., Fukushima H., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 33 （ 1 ） 35 - 38 2024年

ISSN 09185739

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Potential indication of chemotherapy for hypodipsia and arginine vasopressin deficiency secondary to hypothalamic-pituitary Langerhans cell histiocytosis: a case report and literature review

Ota M., Sato T., Nakano S., Yamazaki F., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 33 （ 3 ） 157 - 162 2024年

ISSN 09185739

Hypothalamic-pituitary Langerhans cell histiocytosis (HP-LCH) is often associated with arginine vasopressin deficiency (AVD). Patients with AVD caused by HP-LCH rarely develop an impaired osmotic threshold for thirst (OTT). Improvement in OTT among such patients has not been reported in the literature. To our knowledge, here we report the first case of AVD due to HP-LCH in which hypodipsia resolved during chemotherapy. A nine-year-old Japanese girl presented with polydipsia, polyuria, anorexia, and hypernatremia (149.8 mEq/L) and was diagnosed with AVD secondary to HP-LCH. Visual analog scale examination showed a reduced OTT following the water deprivation test. During chemotherapy for Langerhans cell histiocytosis (LCH), serum sodium concentrations became stable between 138.9 and 142.9 mEq/L under the replacement of desmopressin. Repeated visual analog scale examinations showed that she experienced a sense of thirst at a serum sodium concentration of 142.3–144.6 mEq/L, at which she did not experience any thirst prior to the initiation of chemotherapy. These data suggest that chemotherapy directly improved the OTT in our patient. Improved mechanical compression or infiltration of the hypothalamus related to OTT may lead to the recovery of the sense of thirst. This report highlights the potential role of chemotherapy for solitary HP-LCH in patients with hypodipsia and AVD.

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Characteristic external genitalia in male neonates with 5α-reductase deficiency

Munenaga T., Ichihashi Y., Nakano S., Shibata H., Sato T., Asanuma H., Homma K., Hasegawa T., Ishii T.

Endocrine Journal 71 （ 10 ） 973 - 978 2024年

ISSN 09188959

There have been no reports comparing neonatal external genitalia of 5α-reductase deficiency (5αRD) with those of other 46,XY differences of sex differentiation (DSD). This study enrolled 31 Japanese cases of 46,XY DSD whose external genitalia was examined during the neonatal period; four were diagnosed as 5αRD and 15 were defined as non-5αRD by genetic analysis of SRD5A2 or urinary steroid metabolites. We compared the following characteristics between 5αRD and non-5αRD groups, adjusting the severity of undermasculinization of the external genitalia: stretched penile length (SPL), glans width, location of the external urethral opening, and proportion of undescended testis. The external genitalia of all the 5αRD cases were Quigley classification grade 2 or 3. We compared the phenotypes between the four 5αRD cases and 11 non-5αRD cases with grade 2 or 3. The median (range) of SPL in the 5αRD group (14 mm [11-16]) was significantly lower than that in the non-5αRD group (22 mm [15-29]) (p = 0.003). An SPL cut-off value of <15 mm yielded a sensitivity of 50% (95% confidence interval [CI]; 7–93%) and specificity of 100% (95% CI, 72–100%) for discriminating between the groups. The median glans width, location of the external urethral opening, and proportion of undescended testis were not significantly different between the groups. The SPL of 5αRD in Quigley classification grade 2 or 3 was significantly shorter than that of other 46,XY DSDs with the equivalent grade.

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Sequential imaging of hyperplastic callus formation in Osteogenesis Imperfecta type V: A case report and review of the literature

Yung D., Arai M., Matsumoto S., Sato T., Hirozane T., Yamaguchi S., Asano N., Hasegawa T., Nakayama R.

Journal of Orthopaedic Science 28 （ 6 ） 1430 - 1435 2023年11月

ISSN 09492658

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Fibroblast growth factor 23 levels in cord and peripheral blood during early neonatal period as possible predictors of affected offspring of X-linked hypophosphatemic rickets: Report of three female cases from two pedigrees

Nabeshima Y., Sato T., Zukeran H., Komatsu R., Nakano S., Ichihashi Y., Tominaga T., Miwa M., Amano N., Ishii T., Hasegawa T.

Journal of Pediatric Endocrinology and Metabolism 36 （ 8 ） 786 - 790 2023年08月

ISSN 0334018X

Objectives: The role of serum fibroblast growth factor 23 (FGF23) level in early neonatal period on the diagnosis of X-linked hypophosphatemic rickets (XLH) remains unclear. Case presentation: Two female patients from the first pedigree had an affected mother, and the other female from the second pedigree had an affected father. In all three cases, FGF23 levels were high in cord blood and peripheral blood at day 4-5. Additionally, the FGF23 levels considerably increased from birth to day 4-5. We identified a PHEX pathogenic variant and initiated treatment during infancy in each case. Conclusions: In neonates with a parent diagnosed as PHEX-associated XLH, FGF23 in cord blood and peripheral blood at day 4-5 may be useful markers for predicting the presence of XLH.

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Intracranial germinoma in the lateral ventricle with polydipsia and polyuria: a case report and literature review

Kuranari Y., Miwa T., Kono M., Shibata H., Ishii T., Hasegawa T.

Child's Nervous System 39 （ 4 ） 1065 - 1069 2023年04月

ISSN 02567040

Central nervous system germ cell tumors (CNSGCTs) are rare neoplasms which usually develop in the midline structures. They are occasionally involved in off-midline structures of the brain. Here, we report an extremely rare case of an intracranial germinoma in the lateral ventricle. The patient was a 10-year-old boy with a 1-year history of polydipsia and polyuria. Brain magnetic resonance imaging (MRI) showed a relatively homogeneously enhancing lesion in the lateral ventricle, and the posterior pituitary gland was not hyperintense on T1-weighted imaging. Subependymoma was suspected, and tumor removal operation was performed; however, because the intraoperative pathological investigation revealed germinoma, we could only perform partial removal of the tumor. Postoperative histology also confirmed germinoma. Then, the patient received chemotherapy, followed by radiation therapy. MRI showed no recurrence for 6 years after treatment. Intracranial germinoma in the lateral ventricle is extremely rare. The diagnosis is occasionally challenging, especially when the tumors are located in atypical locations. This paper presents a literature review of previously described CNSGCTs of the lateral ventricle to improve awareness of CNSGCTs in atypical locations. We also consider the relationship between imaging findings and clinical manifestations.

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POU1F1/Pou1f1 c.143-83A > G Variant Disrupts the Branch Site in Pre-mRNA and Leads to Dwarfism

Akiba K., Hasegawa Y., Katoh-Fukui Y., Terao M., Takada S., Hasegawa T., Fukami M., Narumi S.

Endocrinology (United States) 164 （ 2 ） 2023年02月

ISSN 00137227

POU Class 1 Homeobox1 (POU1F1/Pou1f1) is a well-established pituitary-specific transcription factor, and causes, when mutated, combined pituitary hormone deficiency in humans and mice. POU1F1/Pou1f1 has 2 isoforms: the alpha and beta isoforms. Recently, pathogenic variants in the unique coding region of the beta isoform (beta domain) and the intron near the exon-intron boundary for the beta domain were reported, although their functional consequences remain obscure. In this study, we generated mice carrying the Pou1f1 c.143-83A>G substitution that recapitulates the human intronic variant near the exon-intron boundary for the beta domain. Homozygous mice showed postnatal growth failure, with an average body weight that was 35% of wild-type littermates at 12 weeks, which was accompanied by anterior pituitary hypoplasia and deficiency of circulating insulin-like growth factor 1 and thyroxine. The results of RNA-seq analysis of the pituitary gland were consistent with reduction of somatotrophs, and this was confirmed immunohistochemically. Reverse transcription polymerase chain reaction of pituitary Pou1f1 mRNA showed abnormal splicing in homozygous mice, with a decrease in the alpha isoform, an increase in the beta isoform, and the emergence of the exon-skipped transcript. We further characterized artificial variants in or near the beta domain, which were candidate positions of the branch site in pre-mRNA, using cultured cell-basis analysis and found that only c.143-83A>G produced transcripts similar to the mice model. Our report is the first to show that the c.143-83A>G variant leads to splicing disruption and causes morphological and functional abnormalities in the pituitary gland. Furthermore, our mice will contribute understanding the role of POU1F1/Pou1f1 transcripts in pituitary development.

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Fluorodeoxyglucose-positron emission tomography as a potential alternative tool for functional diagnosis of glycogen storage disease type I

Sato T., Inokuchi M., Nakano S., Iwabuchi Y., Hayashida T., Ishii T., Hasegawa T.

Radiology Case Reports 18 （ 1 ） 91 - 93 2023年01月

A 43-year-old woman with genetically confirmed glycogen storage disease type Ib was suspected to have left breast cancer. Fluorodeoxyglucose-positron emission tomography showed high fluorodeoxyglucose accumulation in the whole liver as well as left mammary gland. We consider that high fluorodeoxyglucose accumulation in the liver of patients with glycogen storage disease type I is caused by impaired glucose-6-phosphate metabolism due to the congenital deficiency of glucose-6-phosphatase activities in hepatocytes. This study describes fluorodeoxyglucose-positron emission tomography as a potential alternative tool to diagnose glycogen storage disease type I functionally.

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Clinical features of non-classical 21-hydroxylase deficiency after normal newborn mass screening

Takahashi F., Adachi S., Sakurai N., Mori T., Fujikura K., Usui T., Hasegawa T.

Pediatrics International 65 （ 1 ） 2023年01月

ISSN 13288067

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A girl with type 1A diabetes mellitus and extrahepatic portal vein obstruction

Kameyama M., Sato T., Nakano S., Maeda Y., Yamada Y., Ishii T., Hasegawa T.

Pediatrics International 65 （ 1 ） 2023年01月

ISSN 13288067

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Potential benefit of rapid genetic testing for Pallister–Hall syndrome

Maeda-Usui A., Sato T., Nakano S., Kusakawa M., Kin T., Takahashi N., Motojima Y., Asanuma H., Hida M., Ishii T., Kuroda T., Hasegawa T.

Clinical Pediatric Endocrinology 32 （ 2 ） 119 - 122 2023年

ISSN 09185739

Pallister–Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic GLI3 pathogenic variant. A two-month-old infant was referred to our institution because of undetermined sex. The infant had atypical genitalia with postaxial polysyndactyly, a hypothalamic mass, and an imperforate anus. We identified a known pathogenic variant of the GLI3 gene within one week and diagnosed the infant with PHS. The parents assigned the infant as male, considering the 46,XY karyotype, normal testosterone secretion, possible male identity, and the natural history of PHS. In infants with atypical genitalia and other malformations, such as polydactyly, a hypothalamic mass, or an imperforate anus, rapid GLI3 testing may provide information for planning lifelong management, including sex assignment.

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Pubertal induction in Turner syndrome without gonadal function: A possibility of earlier, lower-dose estrogen therapy

Hasegawa Y., Hasegawa T., Satoh M., Ikegawa K., Itonaga T., Mitani-Konno M., Kawai M.

Frontiers in Endocrinology 14 2023年

Delayed and absent puberty and infertility in Turner syndrome (TS) are caused by primary hypogonadism. A majority of patients with TS who are followed at hospitals during childhood will not experience regular menstruation. In fact, almost all patients with TS need estrogen replacement therapy (ERT) before they are young adults. ERT in TS is administered empirically. However, some practical issues concerning puberty induction in TS require clarification, such as how early to start ERT. The present monograph aims to review current pubertal induction therapies for TS without endogenous estrogen production and suggests a new therapeutic approach using a transdermal estradiol patch that mimics incremental increases in circulating, physiological estradiol. Although evidence supporting this approach is still scarce, pubertal induction with earlier, lower-dose estrogen therapy more closely approximates endogenous estradiol secretion.

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Potential risk of inguinal hernia in complete androgen insensitivity syndrome

Kimizuka Y., Sato T., Nakano S., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 32 （ 1 ） 76 - 78 2023年

ISSN 09185739

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A case of 46,XY complete gonadal dysgenesis with a novel missense variant in SRY

Narita C., Takubo N., Sammori M., Matsumura Y., Shimura K., Ozaki R., Haruna H., Narumi S., Ishii T., Hasegawa T., Shimizu T.

Clinical Pediatric Endocrinology 32 （ 4 ） 235 - 238 2023年

ISSN 09185739

Disorders of sex development (DSD) with mild external genital abnormalities may be diagnosed after puberty. Here, we report a case of 46,XY complete gonadal dysgenesis with a novel missense variant in sex-determining region Y (SRY), diagnosed after primary amenorrhea. A 15-yr-old patient presented to our gynecology department with a chief complaint of amenorrhea. The patient was diagnosed with a 46,XY karyotype, and SRY gene positivity. Gonadotropin levels were high, whereas testosterone levels were low. A pelvic magnetic resonance imaging (MRI) revealed a hypoplastic uterus; however, no gonads could be identified. Laparoscopy revealed bilateral streak gonads, fallopian tube-like structures, and the uterus. The gonads were removed based on the risk of gonadal malignancy. Comprehensive genetic analysis of DSD revealed a previously unreported SRY variant, c.271A>T, p.Ser91Cys, and in silico analysis predicted the variant to be pathogenic. The patient was diagnosed with 46,XY complete gonadal dysgenesis with a novel missense variant in SRY. The patient continued female hormone replacement therapy and experienced breast enlargement and cyclic menstruation. Determining the etiology of DSD can be difficult, causing anxiety in patients and their families. In addition to surgical scrutiny, genetic analysis is important to aid in diagnosis and reassure patients and their families.

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Less-Invasive Diagnostic Approaches for Infants with Suspected Differences of Sex Development: A Case Report of a 297-g Neonate with Ambiguous Genitalia

Sato T., Nakano S., Ichihashi Y., Kobayashi H., Hida M., Ishii T., Hasegawa T.

Neonatology 119 （ 6 ） 785 - 789 2022年12月

ISSN 16617800

Less-invasive diagnostic approaches for low-birthweight preterm neonates with suspected differences of sex development have not been established. Herein, we describe our diagnostic approaches for a 297-g neonate with ambiguous genitalia. Using a fiberscope, the external genitalia were inspected in an incubator to minimize the risk of hypothermia and infection. Endotracheal aspirate, collected during routine care, was used for genetic testing to avoid anemia and vital signs fluctuations caused by peripheral blood sampling. Array comparative genomic hybridization indicated a 46,XY karyotype. No pathogenic variants of AR and SRD5A2 were found. Endocrinological data could not be evaluated owing to the absence of reference data. Identification and structural evaluation of the internal genitalia and gonads were difficult. On postnatal day 42, the parents assigned their baby's sex as male. Our less-invasive diagnostic approaches of inspection and genetic testing are useful for management, including sex assignment in extremely low-birthweight preterm neonates with ambiguous genitalia.

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Continuous glucose monitoring in an infant with panhypopituitarism having hypoglycemia on growth hormone therapy

Kiuchi K., Sato T., Nakano S., Ishii T., Hasegawa T.

Journal of Pediatric Endocrinology and Metabolism 35 （ 12 ） 1556 - 1559 2022年12月

ISSN 0334018X

Objectives: The usefulness of continuous glucose monitoring (CGM) in infants with panhypopituitarism (PH) having hypoglycemia is yet to be explored. The potential adverse effects of growth hormone (GH) replacement therapy, such as hyperglycemia, cannot be comprehensively evaluated using the conventional measurement. Case presentation: A 2-month-old infant with PH, including severe GH deficiency, had hypoglycemia despite frequent feeding. Glucose levels were monitored using CGM before and after GH replacement therapy. The proportion of time for hypoglycemia decreased from 4.9 to 0% (p<0.017). Hyperglycemia did not increase. The CGM method did not contribute to any adverse events requiring intervention. Our patient only experienced minor bleeding and no episode of cellulitis. Conclusions: CGM is useful in controlling glucose levels in infants with hypoglycemia and PH.

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The High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency

Watanabe K., Tsuji-Hosokawa A., Hashimoto A., Konishi K., Ishige N., Yajima H., Sutani A., Nakatani H., Gau M., Takasawa K., Tajima T., Hasegawa T., Morio T., Kashimada K.

Journal of Clinical Endocrinology and Metabolism 107 （ 12 ） 3341 - 3352 2022年12月

ISSN 0021972X

Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Objective: We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo. Methods: Five steroids (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS. Samples from 2 cohorts were assayed: Cohort A, 63 "screening positive"neonates who were referred to an endocrinologist (n = 26 with 21OHD; n = 37 false-positive; obtained from 2015 to 2020); and Cohort B, samples (n = 2014) with 17αOHP values in the 97th percentile or above, in the first-tier test with 17αOHP ELISA from 2020 to 2021. Results: Analysis of Cohort A revealed that the 3 indexes 21DOF, 11DOF/17αOHP, and (4AD + 17αOHP)/F had higher area under the curve (AUC) values (0.999, 0.997, 0.989, respectively), while the 17αOHP AUC was lower (0.970). Accordingly, in addition to 17αOHP, the 3 markers were included for defining the screening algorithm. The assay of Cohort B revealed that the new algorithm gave 92% of predicted positive predictive value without false-negative cases. We also determined the reference values for the 5 steroids at 4 to 7 days after birth, according to sex and gestational age (GA), revealing extremely low levels of 21DOF at any GA irrespective of sex differences. Conclusion: Our study demonstrated the high relevance of 21DOF, (4AD + 17αOHP)/F, and 11DOF/17αOHP, rather than 17αOHP, for 21OHD screening.

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GWAS of thyroid dysgenesis identifies a risk locus at 2q33.3 linked to regulation of Wnt signaling

Narumi S., Opitz R., Nagasaki K., Muroya K., Asakura Y., Adachi M., Abe K., Sugisawa C., Kuhnen P., Ishii T., Nothen M.M., Krude H., Hasegawa T.

Human Molecular Genetics 31 （ 23 ） 3967 - 3974 2022年12月

ISSN 09646906

Congenital hypothyroidism due to thyroid dysgenesis (TD), presented as thyroid aplasia, hypoplasia or ectopia, is one of the most prevalent rare diseases with an isolated organ malformation. The pathogenesis of TD is largely unknown, although a genetic predisposition has been suggested. We performed a genome-wide association study (GWAS) with 142 Japanese TD cases and 8380 controls and found a significant locus at 2q33.3 (top single nucleotide polymorphism, rs9789446: P = 4.4 × 10-12), which was replicated in a German patient cohort (P = 0.0056). A subgroup analysis showed that rs9789446 confers a risk for thyroid aplasia (per allele odds ratio = 3.17) and ectopia (3.12) but not for hypoplasia. Comprehensive epigenomic characterization of the 72-kb disease-associated region revealed that it was enriched for active enhancer signatures in human thyroid. Analysis of chromosome conformation capture data showed long-range chromatin interactions of this region with promoters of two genes, FZD5 and CCNYL1, mediating Wnt signaling. Moreover, rs9789446 was found to be a thyroid-specific quantitative trait locus, adding further evidence for a cis-regulatory function of this region in thyroid tissue. Specifically, because the risk rs9789446 allele is associated with increased thyroidal expression of FDZ5 and CCNYL1 and given the recent demonstration of perturbed early thyroid development following overactivation of Wnt signaling in zebrafish embryos, an enhanced Wnt signaling in risk allele carriers provides a biologically plausible TD mechanism. In conclusion, our work found the first risk locus for TD, exemplifying that in rare diseases with relatively low biological complexity, GWAS may provide mechanistic insights even with a small sample size.

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Whole-exome analysis of 177 pediatric patients with undiagnosed diseases

Narita K., Muramatsu H., Narumi S., Nakamura Y., Okuno Y., Suzuki K., Hamada M., Yamaguchi N., Suzuki A., Nishio Y., Shiraki A., Yamamori A., Tsumura Y., Sawamura F., Kawaguchi M., Wakamatsu M., Kataoka S., Kato K., Asada H., Kubota T., Muramatsu Y., Kidokoro H., Natsume J., Mizuno S., Nakata T., Inagaki H., Ishihara N., Yonekawa T., Okumura A., Ogi T., Kojima S., Kaname T., Hasegawa T., Saitoh S., Takahashi Y.

Scientific Reports 12 （ 1 ） 2022年12月

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

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Fetal growth restriction and a single umbilical artery are independent predictors of hypospadias during pregnancy

Endo T., Iida M., Ichihashi Y., Oishi M., Ikenoue S., Kasuga Y., Sato T., Hida M., Ishii T., Asanuma H., Hasegawa T., Tanaka M., Ochiai D.

Placenta 130 53 - 59 2022年12月

ISSN 01434004

Introduction: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. Methods: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. Results: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50–35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00–139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. Discussion: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

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An elderly patient with 17α-hydroxylase deficiency misdiagnosed as primary aldosteronism: a case report

Ishinoda Y., Uto A., Yamada Y., Okazaki M., Asada H., Wakamatsu S., Kurihara I., Shibata H., Ishii T., Hasegawa T., Kumagai H., Kasuga A.

BMC Endocrine Disorders 22 （ 1 ） 2022年12月

Background: 17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder. Aldosterone levels are usually low in patients with 17OHD. However, among the approximately 150 cases of 17OHD reported to date, aldosterone levels were not low in all cases. Therefore, some 17OHD cases may have been misdiagnosed as primary aldosteronism (PA) cases. Often before puberty, 17OHD is diagnosed because of abnormal genital morphology and menstrual irregularities. However, we report a very rare case of 17OHD in an elderly patient with a high aldosterone/renin ratio (ARR) similar to that in PA. Case presentation: A 63-year-old Japanese woman was transferred to our medical facility for the evaluation of bilateral adrenal hypertrophy, which was incidentally discovered during an abdominal examination after cholecystectomy. The patient had hypokalemia and a high aldosterone/renin ratio. Her medical history included hypertension and right intracerebral capsular hemorrhage at the age of 30 years. Additional testing revealed low cortisol, high adrenocorticotropic hormone, and low testosterone and dehydroepiandrosterone sulfate, indicating congenital adrenal hyperplasia. Genetic analysis revealed a mutation in the CYP17A1 gene and a karyotype of 46, XY; hence, she was diagnosed with 17OHD. Conclusion: 17OHD can resemble PA. The combination of a high ARR and low cortisol level should trigger the consideration of 17OHD.

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Impact of school closure due to the coronavirus disease 2019 pandemic on body mass index in Japanese children: Retrospective longitudinal study

Nagashima Y., Inokuchi M., Yasui Y., Uchida K., Tokumura M., Hasegawa T.

Journal of Paediatrics and Child Health 58 （ 10 ） 1841 - 1846 2022年10月

ISSN 10344810

Aim: During the coronavirus disease 2019 pandemic, the governments of many countries responded to high levels of infection with lockdowns. As a result, some children were reported to experience weight gain. The aim of the present study was to examine the impact of school closures on body mass index (BMI) in Japanese children. Methods: This was a retrospective study of students enrolled in the participating schools (6- to 11-year-old elementary school students and 12- to 14-year-old junior high school students) between 2015 and 2020. Using school health check-up data, annual changes in the BMI standard deviation score (ΔBMI-SDS) were calculated. We compared ΔBMI-SDS in 2019–2020 with the corresponding control years. Results: 19 565 children with complete data were included in the analysis. Median ΔBMI-SDS in 2019–2020 were 0.24–0.35 in elementary school boys, 0.10–0.13 in junior high school boys, −0.02 to 0.15 in elementary school girls and −0.14 to −0.10 in junior high school girls. In comparison with every control year, ΔBMI-SDS in 2019–2020 were significantly higher in elementary school boys (control years: −0.07 to 0.14) and junior high school boys (control years: −0.04 to 0.06), and significantly lower in junior high school girls (control years: −0.06 to 0.09). Conclusion: BMI-SDS increased significantly in elementary and junior high school boys, but decreased significantly in junior high school girls. The pandemic appears to have had an impact on Japanese children that was different from other countries.

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A patient with congenital hypothyroidism due to a PAX8 frameshift variant accompanying a urogenital malformation

Tanase-Nakao K., Muroya K., Adachi M., Abe K., Hasegawa T., Narumi S.

Clinical Pediatric Endocrinology 31 （ 4 ） 250 - 255 2022年10月

ISSN 09185739

PAX8 is a transcription factor that is expressed in the thyroid gland and kidneys. Monoallelic loss-of-function PAX8 variants cause congenital hypothyroidism (CH), and urogenital malformations are infrequent complications seen in less than 10% of PAX8 variant carriers. Herein, we report the case of a 3-yr-old female patient with CH who was diagnosed during newborn screening. She was treated with levothyroxine, and she showed normal growth and development at a minimal dose (0.7 µg/kg/d of levothyroxine at 3 yr of age). At 5 mo of age, she visited an emergency department for fever and was incidentally found to have differently sized kidneys by ultrasonography, which was subsequently diagnosed as unilateral multicystic dysplastic kidney. Her serum creatinine and cystatin C levels were normal. Next-generation sequencing-based genetic analysis revealed that the patient was heterozygous for a PAX8 frameshift variant (p.Thr320ProfsTer106) and a DUOX2 missense variant (p.Arg885Gln). Our patient is the first truncating PAX8 variant carrier to have a urogenital malformation with CH. Genetic analysis for PAX8 should be considered in patients with CH and urogenital malformations.

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Molecular Basis for Hypochondroplasia in Japan

Ishii T., Takagi M., Nagasaki K., Ohara T., Miyai K., Kosho T., Takada F., Nishimura G., Hasegawa T.

Endocrines 3 （ 3 ） 428 - 432 2022年09月

Hypochondroplasia is an autosomal dominant genetic disorder due to a heterozygous pathogenic variant of the FGFR3 gene. The early diagnosis of hypochondroplasia is necessary, since growth hormone is effective for improving adult height. The genetic test for the FGFR3 gene could help the early diagnosis. The detailed characteristics of FGFR3 genotypes have not been widely investigated in Japan, except for a common pathogenic variant, p.Asn540Lys. This study retrospectively analyzed the FGFR3 genotypes of 35 patients from 30 families with hypochondroplasia (age, range 0–6 years, median 1 year) in Japan. The pathogenic variants of FGFR3 were identified in all the patients: p.Asn540Lys in 23 probands (76.7%), p.Lys650Gln in 2 (6.7%), p.Leu324His in 2 (6.7%), p.Leu324Val, p.Ser351Cys, and p.Lys650Thr in 1 each (3.2%). The median age at diagnosis, height SD score at diagnosis, or the severity of radiologic findings was not significantly different between probands with p.Asn540Lys and those with other variants. Intellectual disability or epilepsy was identified in seven patients with p.Asn540Lys, but none with other variants. The genetic test of FGFR3 can be useful for assessing the potential risk of neurological sequela in children with hypochondroplasia.

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High-dose fludrocortisone therapy was transiently required in a female neonate with 21-hydroxylase deficiency

Kawasaki Y., Sato T., Nakano S., Usui T., Narumi S., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 31 （ 2 ） 93 - 97 2022年04月

ISSN 09185739

For salt-wasting 21-hydroxylase deficiency (21OHD), fludrocortisone (FC) is usually supplemented at 0.05–0.2 mg/d dose. To date, no report has described 21OHD neonates requiring > 0.4 mg/d of FC. Our female 21OHD patient was lethargic and experienced weight loss with hyponatremia (133 mEq/L), hyperkalemia (6.5 mEq/L), and elevated active renin concentration (ARC, 1942.2 pg/mL) at 6 days of life. Hydrocortisone and FC replacement were initiated. FC dose was gradually increased to 0.4 mg/d at 21 days of life, but her hyperkalemia (6.4 mEq/L) and high ARC (372.3 pg/mL) persisted. We increased FC to 0.6 mg/d and used a low-potassium and high-sodium formula. Hyperkalemia subsequently improved. At 33 days of life, the ARC decreased to 0.6 pg/mL and FC dosage was gradually decreased. At 3 months of age, the low-potassium and high-sodium formula was discontinued, but the serum potassium level was normal and ARC remained low at 0.1 mg/d of FC. We speculated that severe mineralocorticoid resistance was the reason why her hyperkalemia persisted even with 0.4 mg/d of FC; however, the pathophysiology of transiently severe resistance to FC in this patient is unknown. In conclusion, 21OHD neonates may show severe salt-wasting that transiently require > 0.4 mg/d of FC.

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Destructive thyroiditis without autoantibodies in an infant

Ichikawa Y., Sato T., Ichihashi Y., Ishii T., Hasegawa T.

Pediatrics International 64 （ 1 ） 2022年01月

ISSN 13288067

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Iatrogenic Cushing syndrome due to topical corticosteroids after skin graft surgery for giant nevus: A case report

Katsura M., Sato T., Morita K., Ishii T., Kishi K., Hasegawa T.

Pediatric Dermatology 39 （ 1 ） 147 - 148 2022年01月

ISSN 07368046

Iatrogenic Cushing syndrome (ICS) may be caused by exposure to corticosteroid therapy. We report a case of ICS caused by topical corticosteroids applied to the skin after skin graft surgery. We presume that the development of ICS, in this case, was attributed to a combination of skin barrier disruption, usage of high-potency corticosteroids, broad application area/ large quantity of the corticosteroid, and the extended treatment period. Patients may be at risk for ICS after extensive skin graft surgery if large amounts of very potent topical corticosteroids are applied for an extended period to prevent scar formation or relieve itching.

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Biallelic PROKR2 variants and congenital hypogonadotropic hypogonadism: a case report and a literature review

Sugisawa C., Taniyama M., Sato T., Takahashi Y., Hasegawa T., Narumi S.

Endocrine Journal 69 （ 7 ） 831 - 838 2022年

ISSN 09188959

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that causes gonadotropin-releasing hormone (GnRH) deficiency and sexual immaturity. CHH may accompany an abnormal sense of smell (Kallmann syndrome, KS) or no such manifestation (normosmic-CHH). This unusual combination of manifestations is explained by the fact that GnRH neurons originate in the olfactory placode and migrate to the forebrain during embryogenesis. We describe the case of a 31-year-old man with normosmic-CHH, who also had obesity, type 2 diabetes and intellectual disability. He was noticed to have sexual immaturity (small testes with no pubic hair) at age 20 years, when diabetic ketoacidosis developed. Basal and GnRH-stimulated levels of LH (1.0→12.0 IU/L) and FSH (1.9→6.1 IU/L) were detectable but low. The results of the T&T olfactometer and the Alinamin test were definitely normal, with an anatomically normal olfactory system on MRI. Sequencing of 22 CHH-related genes was performed, and compound heterozygous PROKR2 variants were identified: one was a previously known loss-of-function variant (p.Trp178Ser) and the other was a nonsense variant (p.Trp212*). Through a literature review, we found 22 patients (including our patient) with CHH due to biallelic PROKR2 variants, which led us to recognize that most of the patients (86%) were diagnosed with KS. Clinical observations in this study indicate that, even though they have CHH, biallelic PROKR2 variant carriers may have a normal olfactory system as well as presumably normal migration of GnRH neurons. This suggests that the PROK2-PROKR2 pathway affects the function of GnRH neurons after their migration.

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Transient central diabetes insipidus after cranioplasty for craniosynostosis in an infant with septo-optic dysplasia

Fukuyama T., Sato T., Nakano S., Tomita K., Sakamoto Y., Miwa T., Hamada J., Futagawa N., Hasegawa K., Ishii T., Hasegawa T.

Clinical Pediatric Endocrinology 31 （ 1 ） 50 - 53 2022年

ISSN 09185739

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Reference values of inside leg length and inside leg length to stature ratio for Japanese children, 0–12 years of age

Inokuchi M., Matsuo N., Takayama J.I., Hasegawa T.

Annals of Human Biology 49 （ 1 ） 1 - 9 2022年

ISSN 03014460

Background: Large datasets of detailed anthropometric measurements are scarce in children. The Japanese Standard Association 1978–1981 survey provides a rare opportunity to use high quality data from Japanese children. Aim: To construct inside leg length (ILL) and inside leg length to stature ratio (ILL/S) reference centile curves for Japanese children. Subjects and methods: The study sample consisted of 14,825 boys and 14,577 girls age 0–18 years for stature and weight measurements, and 9064 boys and 8796 girls age 0–12 years for ILL measurements, who participated in the 1978–1981 national survey on body sizes. LMS method was used to construct the reference centile curves. The reference centile curves for stature, weight, ILL, and ILL/S were compared to those of British children. Results: The L, M, and S reference values for Japanese children are presented for stature, weight, ILL, and ILL/S. Compared with British children of 0–12 years of age, Japanese children of 0–12 years of age had shorter median stature, shorter median ILL, and shorter median ILL/S. Conclusion: We present the first reference values for ILL and ILL/S in Japanese children. Japanese children had relatively shorter legs compared to British children from infancy.

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Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021

Naruse M., Katabami T., Shibata H., Sone M., Takahashi K., Tanabe A., Izawa S., Ichijo T., Otsuki M., Omura M., Ogawa Y., Oki Y., Kurihara I., Kobayashi H., Sakamoto R., Satoh F., Takeda Y., Tanaka T., Tamura K., Tsuiki M., Hashimoto S., Hasegawa T., Yoshimoto T., Yoneda T., Yamamoto K., Rakugi H., Wada N., Saiki A., Ohno Y., Haze T.

Endocrine Journal 69 （ 4 ） 327 - 359 2022年

ISSN 09188959

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.

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Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan

Isojima T., Hasegawa T., Yokoya S., Tanaka T.

Endocrine Journal 69 （ 8 ） 927 - 939 2022年

ISSN 09188959

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus–pituitary area in 1.7%, CNS tumor distant from the hypothalamus–pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor–1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, –2.76, –1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

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Current status of transition medicine for 21-hydroxylase deficiency in Japan: from the perspective of pediatric endocrinologists

Takasawa K., Nakamura-Utsunomiya A., Amano N., Ishii T., Hasegawa T., Hasegawa Y., Tajima T., Ida S.

Endocrine Journal 69 （ 1 ） 75 - 83 2022年

ISSN 09188959

To manage of 21-hydroxylase deficiency (21-OHD), transition medicine from pediatric to adult health care is an important process and requires individually optimized approaches. We sent cross-sectional questionnaire surveys on the current status of transition from pediatric to adult health care in 21-OHD patients to all councillors of the Japanese Society for Pediatric Endocrinology. Many pediatric departments (42.2%) experienced adult 21-OHD patients, and 115 patients (53 males, mean age of 26) in 46 institutions were identified. Whereas almost two-thirds of pediatric endocrinologists regarded the problems of counterparts and cooperation as hindrance of transition medicine, the major reason for continuing to be treated in pediatrics was the patient’s own request. The prevalence of long-term complications including obesity, osteoporosis, infertility, menstrual disorder, gender dysphoria, and testicular adrenal rest tumor were 27.5%, 8.8%, 11.1%, 26.3%, 7.1%, 12.5%, respectively, which is comparable to those of other cohorts previously reported. However, several items, especially infertility and osteoporosis were not checked well enough in adult 21-OHD patients treated in pediatrics. Though 44 of 62 female patients had genital reconstructive surgery, more than half of them were not followed up by gynecologists or pediatric urologists. Quite a few adult 21-OHD patients had been followed up in pediatrics even after coming of age; however, surveillance by pediatric endocrinologists of gynecological, reproductive, and mental problems may be insufficient. Therefore, multidisciplinary approaches should be required in transition medicine for 21-OHD and prerequisite for graduation of pediatrics. Pediatric endocrinologists will need to play a leading role in the development of transition systems.

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Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency

Higa M., Zaha A., Takushi A., Morishima N., Majikina T., Touma T., Shimabukuro M., Masuzaki H., Honda M., Hasegawa T.

Human Genome Variation 8 （ 1 ） 2021年12月

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Hereditary paraganglioma presenting with atypical symptoms: Case report

Eguchi S., Ono R., Sato T., Yada K., Umehara N., Narumi S., Ichihashi Y., Nozaki T., Kanomata N., Hasegawa T., Ozawa M., Hasegawa D.

Medicine (United States) 100 （ 46 ） 2021年11月

ISSN 00257974

Rationale:Paraganglioma (PGL), an extra-adrenal pheochromocytoma, is a rare tumor, especially in children. While hypersecretion of catecholamines causes the classic triad of headaches, palpitations, and profuse sweating, prompt diagnosis is still challenging.Patient concerns:For 7 months, an 8-year-old boy complained of polyuria and weight loss, followed by proteinuria and headache for 1 month prior to admission. He was admitted to our hospital due to an afebrile seizure.Diagnosis:His blood pressure remained markedly elevated even after cessation of the convulsion. Magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Abdominal computed tomography showed a mass lesion encasing the left renal artery, measuring 41 mm in length along its major axis. The plasma and urine levels of normetanephrine were elevated. Additionally, iodine-123-metaiodobenzylguanidine scintigraphy showed an abnormal uptake in the abdominal mass with no evidence of metastasis. Based on these findings, we tentatively diagnosed him with PGL.Intervention:Substantial alpha-and beta-blocking procedures were performed, followed by a tumor resection and an extended left nephrectomy on day 31 of hospitalization. Pathological findings confirmed the diagnosis of PGL.Outcome:The postoperative course was uneventful, and his blood pressure normalized without the use of antihypertensive agents. Genetic testing revealed a known SDHB germline mutation. The same mutation was also detected on his father and paternal grandfather without any history of hypertension or malignant tumor.Lesson:It remains challenging to diagnose pheochromocytoma/paraganglioma (PPGL) promptly because PPGL can present with a variety of symptoms. Preceding symptoms of the presented case might be caused by PGL. Although PPGL is a rare disease, especially in children, it should be considered in differential diagnosis when various unexplained symptoms persist.

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Two girls with a neonatal screening-negative 21-hydroxylase deficiency requiring treatment with hydrocortisone for virilization in late childhood

Onuma S., Fukuoka T., Miyoshi Y., Fukui M., Satomura Y., Yasuda K., Kimura T., Tachibana M., Bessho K., Yamamoto T., Tanaka H., Katsumata N., Fukami M., Hasegawa T., Ozono K.

Clinical Pediatric Endocrinology 30 （ 3 ） 143 - 148 2021年07月

ISSN 09185739

Herein, we report two girls with a neonatal screening (NS)-negative 21-hydroxylase deficiency (21-OHD) requiring treatment with hydrocortisone due to virilization that developed in late childhood. Patient 1 was born prematurely on the 30th gestational week with normal external genitalia at birth. She passed the NS for 21-OHD. At 6 yr of age, she was referred to a hospital for evaluation of premature pubarche and clitoromegaly. Her diagnosis was central precocious puberty, and GnRH agonist was initiated. However, her symptoms did not improve despite treatment for over 4 years. She was then referred to our hospital where she was diagnosed with 21-OHD. Although she was started on hydrocortisone therapy, her adult height reached only 140 cm (−3.4 SD). Patient 2 was delivered at 37 weeks of gestation and passed the NS for 21-OHD. She was referred to a hospital because of premature pubarche at the age of 6 yr. She was diagnosed with 21-OHD, and hydrocortisone replacement therapy was initiated. Her present height at 13 yr of age is 148 cm (−1.3 SD). These cases reminded us that the possibility of 21-OHD should be considered when patients show premature pubarche or precocious puberty, even if they passed the NS test for 21-OHD.

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Identification of the first promoter-specific gain-of-function SOX9 missense variant (p.E50K) in a patient with 46,XX ovotesticular disorder of sex development

Ushijima K., Ogawa Y., Terao M., Asakura Y., Muroya K., Hayashi M., Ishii T., Hasegawa T., Sekido R., Fukami M., Takada S., Narumi S.

American Journal of Medical Genetics, Part A 185 （ 4 ） 1067 - 1075 2021年04月

ISSN 15524825

SOX9, a transcription factor, is expressed in the undifferentiated XX and XY gonads. SRY induces significant upregulation of SOX9 expression in XY gonads. Loss-of-function SOX9 variants cause testicular dysgenesis in 46,XY patients, while duplication of the total gene or the upstream regulatory region results in testicular development in 46,XX patients. However, gain-of-function (GoF) SOX9 variants have not been reported previously. We report the case of a 16-year-old female patient with a 46,XX karyotype who had masculinized external genitalia and unilateral ovotestis. Next-generation sequencing-based genetic screening for disorders of sex development led to the identification of a novel SOX9 variant (p.Glu50Lys), transmitted from the phenotypically normal father. Expression analysis showed that E50K-SOX9 enhanced transactivation of the luciferase reporter containing the testis enhancer sequence core element compared with that containing the wildtype-SOX9. This GoF activity was not observed in the luciferase reporter containing Amh, the gene for anti-Müllerian hormone. We genetically engineered female mice (Sox9E50K/E50K), and they showed no abnormalities in the external genitalia or ovaries. In conclusion, a novel SOX9 variant with a promoter-specific GoF activity was identified in vitro; however, the disease phenotype was not recapitulated by the mouse model. At present, the association between the GoF SOX9 variant and the ovotestis phenotype remains unclear. Future studies are needed to verify the possible association.

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An infant with congenital nephrogenic diabetes insipidus presenting with hypercalcemia and hyperphosphatemia

Tao K., Awazu M., Honda M., Shibata H., Mori T., Uchida S., Hasegawa T., Ishii T.

Endocrinology, Diabetes and Metabolism Case Reports 2021 （ 1 ） 2021年04月

We report a male infant with congenital nephrogenic diabetes insipidus (NDI) who presented with hypercalcemia and hyperphosphatemia since birth. Serum sodium started to increase at 39 days. Although there was no polyuria, urine osmolality was 71 mOsm/kg, when serum osmolality was 296 mOsm/kg with plasma arginine vasopressin 22.5 pg/mL. He was thus diagnosed as NDI. An undetectable level of urine calcium and unsuppressed intact parathyroid hormone suggested hyperparathyroidism including calcium-sensing receptor mutations that could cause hypercalcemia-induced NDI. Polyuria became apparent after the initiation of i.v. infusion for the treatment of hypernatremia. Low calcium and low sodium formula with hypotonic fluid infusion did not correct hypernatremia, hypercalcemia, or hyperphosphatemia. Hydrochlorothiazide and subsequently added celecoxib effectively decreased urine output and corrected electrolytes abnormalities. Normal serum electrolytes were maintained after the discontinuation of low calcium formula. The genetic analysis revealed a large deletion of the arginine vasopressin receptor-2 (AVPR2) gene but no pathogenic variant in the calcium-sensing receptor (CASR) gene. Whether hypercalcemia and hyperphosphatemia were caused by dehydration alone or in combination with other mechanisms remains to be clarified.

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Population-based waist circumference reference values in Japanese children (0-6 years): Comparisons with Dutch, Swedish and Turkish preschool children

Hasegawa T., Inokuchi M., Matsuo N., Takayama J.I.

Journal of Pediatric Endocrinology and Metabolism 34 （ 3 ） 349 - 356 2021年03月

ISSN 0334018X

Background: During 1978-1981 the Japanese Standards Association conducted a national survey to collect 64 distinct body measurements for Japanese children and adults. During 1978-1981, the prevalence of childhood obesity was relatively low yet the population was well nourished in Japanese children. The aim of this study is to construct waist circumference and waist circumference to stature ratio reference centile curves for Japanese preschool children. Methods: We utilized 1978-1981 national survey data on body sizes. There are 4937 boys and 4758 girls age 0-6 years for waist circumference measurements. Waist circumference was measured at the level of the umbilicus. Using LMS method, centile curves were constructed for waist circumference and waist circumference to stature ratio. These reference values were compared with those of Dutch, Swedish and Turkish children. Results: Centile reference curves were made for clinical and epidemiological use. Japanese children had smaller waist circumference centile values as compared to waist circumference measured at the midpoint of the lowest rib cage and the iliac crest of Dutch, Swedish and Turkish children. However, Japanese children had comparable waist circumference to stature ratio centile values to those of Dutch and Turkish children. Conclusions: This study presents the first age-, sex-, and ethnicity-specific reference values for waist circumference and waist circumference to stature ratio in Japanese preschool children.

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A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling

Suda K., Fukuoka H., Iguchi G., Kanie K., Fujita Y., Odake Y., Matsumoto R., Bando H., Ito H., Takahashi M., Chihara K., Nagai H., Narumi S., Hasegawa T., Ogawa W., Takahashi Y.

Journal of Clinical Endocrinology and Metabolism 106 （ 3 ） 718 - 723 2021年03月

ISSN 0021972X

Context: Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. Case Description: A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T>A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. Conclusion: This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.

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Oral sodium phenylbutyrate for hyperammonemia associated with congenital portosystemic shunt: A case report

Hasegawa T., Sato T., Ishii T., Oyanagi T., Kato M., Kuroda T., Nakatsuka S.

Journal of Pediatric Endocrinology and Metabolism 34 （ 3 ） 407 - 410 2021年03月

ISSN 0334018X

Objectives: The efficacy of sodium phenylbutyrate (SPB) for hyperammonemia associated with congenital portosystemic shunt (CPSS) remains unknown. We show the effectiveness of oral SPB. Case presentation: Our patient had CPSS with severe hypoplasia of extrahepatic portal veins. At 9 months of age, to assess the efficacy of oral SPB, we evaluated the 24 h fluctuations of venous ammonia levels. In the first two days without SPB, ammonia levels were above 80 μmol/L for half a day. On the third and fourth days, administration of oral SPB three times a day decreased ammonia to acceptable levels, except at midnight. On the fifth day, another oral SPB administration at 8 pm decreased ammonia at midnight. Low levels of branched-chain amino acids, as well as coagulation disturbances, were observed without apparent symptoms. At 12 months of age, he showed normal psychomotor development. Conclusions: Oral SPB may be effective for hyperammonemia associated with CPSS.

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The progression of salt-wasting and the body weight change during the first 2 weeks of life in classical 21-hydroxylase deficiency patients

Gau M., Konishi K., Takasawa K., Nakagawa R., Tsuji-Hosokawa A., Hashimoto A., Sutani A., Tajima T., Hasegawa T., Morio T., Kashimada K.

Clinical Endocrinology 94 （ 2 ） 229 - 236 2021年02月

ISSN 03000664

Background: One of the major purposes of newborn screening for 21-hydroxylase deficiency (21OHD) is preventing life-threatening adrenal crisis. However, the details of adrenal crisis in newborns are not precisely documented. Aim: We aimed to clarify the clinical details of salt-wasting in newborn 21OHD patients. Methods: Based on the follow-up survey of the screening in Tokyo from 1989 to 2017, we retrospectively analysed the conditions of classical 21OHD neonates before the initiation of therapy. Results: One hundred classical 21OHD patients (55 male, 45 female) were analysed. The age at the first hospital visit was 0–20 days with sex difference (male: 9.0 ± 3.5 days; female: 6.2 ± 3.9 days). Thirty-seven (37.4%) patients exhibited severe salt-wasting (SSW), that is, Na < 130 mEq/L, K > 7 mEq/L or Na/K ratio < 20; except for one case, SSW developed in or after the second week of life. The serum concentrations of Na, K and Na/K were linearly correlated with age in days (R2 =.38,.25, and.34 respectively), suggesting that the risk of SSW increases linearly without a threshold. The age at which the regression lines reached Na < 130 mEq/L, K > 7 mEq/L and Na/K < 20 was approximately coincided, 11.1, 12.3 and 11.2 days, respectively. All SSW patients exhibited decreased body weight from birth in their second week of life. Conclusion: Our data revealed that the risk of developing SSW increases during the second week of life without a threshold, and for preventing SSW, early intervention, ideally during first week of life, is desirable. An increased body weight in the second week of life indicates the absence of SSW.

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Case Report: Prenatal Genetic Counseling to Parents of Fetuses Suspected of Having Ambiguous Genitalia

Sato T., Ishii T., Yamaguchi Y., Ichihashi Y., Ochiai D., Asanuma H., Kuroda T., Hasegawa T.

Frontiers in Pediatrics 8 2021年01月

The occurrence of fetuses suspected of having ambiguous genitalia will likely increase in the future. Currently, the impact of prenatal genetic counseling on parents' understanding and psychological preparedness has not been addressed. We provided prenatal genetic counseling to parents of two fetuses suspected of ambiguous genitalia. Case 1: At 22 weeks of gestation, swelling of the labia majora, and a clitoris-like structure were noted despite 46,XY detected in amniotic fluid cells. Case 2: At 28 weeks of gestation, bladder exstrophy and a scrotum-like structure were noted. At 32 weeks (Case 1) and 37 weeks (Case 2) of gestation, we shared information with parents regarding the possible difficulty of legal sex assignment at birth, and a scenario for registration of the birth certificate. At birth, both babies presented with ambiguous genitalia. For both cases, the parents remained calm on seeing their baby's genitalia for the first time. After a month, we shared medical information with parents, including karyotype, testosterone production capacity, and surgical schedule. In both cases parents assigned their respective baby's legal sex as male. Several months later, parents were questioned on prenatal genetic counseling. Case 1: Mother, “I was prepared to address our baby's genitalia calmly.” Father, “I understood the procedure of legal sex assignment.” Case 2: Mother, “Without counseling, I would have been more upset and worried.” Father, “We were assured that multidisciplinary experts would support us.” Prenatal genetic counseling provides reassurance to parents, who remain informed and emotionally secure throughout the legal sex assignment of their child.

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Inactivation of a Frameshift TSH Receptor Variant Val711Phefs∗18 is Due to Acquisition of a Hydrophobic Degron

Sugisawa C., Ono M., Kashimada K., Hasegawa T., Narumi S.

Journal of Clinical Endocrinology and Metabolism 106 （ 1 ） E265 - E272 2021年01月

ISSN 0021972X

Context: Inactivating variants of thyrotropin (thyroid-stimulating hormone; TSH) receptor (TSHR) cause congenital hypothyroidism. More than 60 such variants have been reported so far, most of which were located in the extracellular or transmembrane domain. Objective: We report the identification and characterization of a frameshift TSHR variant in the intracytoplasmic C-tail region. Methods: Sequencing of TSHR was performed in a patient with congenital hypothyroidism. The functionality of the identified variants was assessed by expressing TSHR in HEK293 cells and measuring TSH-dependent activation of the cAMP-response element-luciferase reporter. A series of systematic mutagenesis experiments were performed to characterize the frameshifted amino acid sequence. Results: The proband was heterozygous for a known TSHR variant (p.Arg519His) and a novel frameshift TSHR variant (p.Val711Phefs∗18), which removed 54 C-terminal residues and added a 17-amino acid frameshifted sequence. The loss of function of Val711Phefs∗18-TSHR was confirmed in vitro, but the function of Val711∗-TSHR was found to be normal. Western blotting showed the low protein expression of Val711Phefs∗18-TSHR. Fusion of the frameshift sequence to green fluorescent protein or luciferase induced inactivation of them, indicating that the sequence acted as a degron. A systematic mutagenesis study revealed that the density of hydrophobic residues in the frameshift sequence determined the stability. Eight additional frameshift TSHR variants that covered all possible shifted frames in C-tail were created, and another frameshift variant (Thr748Profs∗27) with similar effect was found. Conclusions: We characterized a naturally occurring frameshift TSHR variant located in C-tail, and provided a unique evidence that hydrophobicity in the C-terminal region of the receptor affects protein stability.

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Complete androgen insensitivity syndrome with accelerated onset of puberty due to a sertoli cell tumor

Izawa M., Hisamatsu E., Yoshino K., Yoshida M., Sato T., Narumi S., Hasegawa T., Hamajima T.

Clinical Pediatric Endocrinology 30 （ 2 ） 99 - 104 2021年

ISSN 09185739

Complete androgen insensitivity syndrome (CAIS) is caused by mutations in the androgen receptor gene. Patients with this syndrome have a 46,XY karyotype, male gonads, and normal female external genitalia. While the pre-pubertal risk of developing gonadal tumors is low in these patients, it increases with age. Most gonadal tumors arise from germ cells; stromal cell tumors are uncommon. Herein, we report a CAIS patient with a feminizing Sertoli cell tumor. The patient presented at 8 yr of age with breast enlargement and growth acceleration, concomitant with elevated serum estradiol levels and suppressed serum gonadotropin levels; these findings were inconsistent with CAIS. The patient underwent gonadectomy at 10 yr of age, and histology demonstrated presence of a non-malignant Sertoli cell tumor in the right gonad. We conclude that this is the first reported case of CAIS with accelerated onset of puberty resulting from a Sertoli cell tumor.

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The first survey about women doctors in the japanese society for pediatric endocrinology (Jspe)

Murashita M., Ito J., Hasegawa T.

Clinical Pediatric Endocrinology 30 （ 3 ） 121 - 126 2021年

ISSN 09185739

The Career Development for Women Pediatric Endocrinologists and Work-Life Balance Committee and Support Team for Women Doctors in Education and Training Committee investigated the current situation of women doctors in the Japanese Society for Pediatric Endocrinology (JSPE). The proportion of women doctors (PWD) was as follows. 1) Members of JSPE: 40.2% in fiscal 2018, versus 33.3% in fiscal 2010; 2) councilors: 21.6% from fiscal 2014 to 2017, versus 6.3% from fiscal 2008 to 2010; 3) board members: 13.6% from fiscal 2014 to 2017, versus 0% from fiscal 2008 to 2010; 4) board-certified endocrinologists (Pediatrics) and certified endocrine educators (Pediatrics): 31.7% and 25.4% in fiscal 2018, versus 22.4% and 15.3% in fiscal 2010, respectively; and 5) average value of first presenters and chairpersons in the Annual Scientific Meeting of JSPE was 41.4% and 22.3% from 2010 to 2019. These PWD figures for JSPE were higher than those of the Japan Pediatric Society and the Japan Endocrine Society, indicating a reducing gender gap in JSPE, although increases in the PWD of decision-making posts remains insufficient.

Access to Document (DOI)

The current status of 492 adult women with turner syndrome: A questionnaire survey by the foundation for growth science

Hanew K., Tanaka T., Horikawa R., Hasegawa T., Yokoya S.

Endocrine Journal 68 （ 9 ） 1081 - 1089 2021年

ISSN 09188959

Current status and its background of Adult Turner Syndrome (TS) are not clarified well. Via a questionnaire survey of 492 adult women with TS, this study investigated the association between menstruation, Kaufmann therapy (menstrual induction therapy), social status (education, employment & marriage), complications, transition from pediatric to adult care, and sex chromosome karyotype using statistical methods. Spontaneous menarche occurred in 22.0% and more frequently among patients with the 45,X/46,XX karyotype. Over 60% of these subjects, menstruation did not persist regularly. Kauffmann therapy was performed in 69.4%; the most common formulation was a conjugated estrogen and progesterone combination. Marriage and higher education advancement rates were low in adults with TS, whereas their employment rate was similar to that of the age-matched general female population. Patients receiving Kauffmann therapy had higher complication rates, greater education length, and higher employment rates. The higher-education advancement rate was observed among patients with 45,X/46,X,Xi and 46,X,Xi karyotypes. Transition from pediatrician to adult specialist was not smooth, subjects were treated in pediatric departments (60.7%), gynecological department (21.4%), internal medicine departments (13.3%), and others. While reason is not clear, the largest number of TS patients are treated in general pediatrics and the percentage of receiving Kauffmann therapy and having complication were significantly lower than in pediatric and adult department of endocrinology (& metabolism). This Study revealed many novel findings of adult TS.

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Adenocorical cartinoma characterized by gynecomastia: A case report.

Takeuchi T, Yoto Y, Ishii A, Tsugawa T, Yamamoto M, Hori T, Kamasaki H, Nogami K, Oda T, Nui A, Kimura S, Yamagishi T, Homma K, Hasegawa T, Fukami M, Watanabe Y, Sasamoto H, Tsutsumi H.

Clin Pediatr Endocrinol 27 9-18 2018年

研究論文（学術雑誌）, 共著, 査読有り

Comparison of serum 25-hydroxyvitamin D levels between radioimmunoassay and liquid chromatography tandem mass spectrometry in infants and postpartum women.

Hara K, Ikeda K, Hasegawa T.

J Pediatr Endocrinol Metab 2018年

研究論文（学術雑誌）, 共著, 査読有り

Rapid Growth and Early Metastasis of Papillary Thyroid Carcinoma in an Adolescent Girl with Graves’ Disease.

Shimura K, Shibata H, Mizuno Y, Amano N, Hoshino K, Kuroda T, Kameyama K, Matsuse M, Mitsutake N, Sugino K, Noh JY, Hasegawa T, Ishii T.

Hor Res Paediatr 2018年

研究論文（学術雑誌）, 共著, 査読有り

A novel truncating mutation in MYH3 causes spondylocarpotarsal synostosis syndrome with basilar invagination.

Takagi M, Shimomura S, Fukuzawa R, Narumi S, Nishimura G, Hasegawa T.

J Hum Genet 2018年

研究論文（学術雑誌）, 共著, 査読有り

A Novel Mutation in NKX2.1 Shows Dominant-Negative Effects Only in the Presence of PAX8

Shinohara H, Takagi M, Ito K, Shimizu E, Fukuzawa R, Hasegawa T.

28 1071-1073 2018年

研究論文（学術雑誌）, 共著, 査読有り

Methylome analysis of thyroid ectopy showed no disease-specific DNA methylation signature.

Narumi S, Matsubara K, Ishii T, Hasegawa T.

Clin Pediatr Endocrinol 2018年

研究論文（学術雑誌）, 共著, 査読有り

A familial case of spondyloepiphyseal dysplasia tarda caused by a novel splice site mutation in TRAPPC2.

Fukuma M, Takagi M, Shimazu T, Imamura H, Yagi H, Nishimura G, Hasegawa T.

Clin Pediatr Endocrinol 27 193-196 2018年

研究論文（学術雑誌）, 共著, 査読有り

A novel truncating mutation in MYH3 causes spondylocarpotarsal synostosis syndrome with basilar invagination.

Takagi M, Shimomura S, Fukuzawa R, Narumi S, Nishimura G, Hasegawa T.

J Hum Genet 2018年

研究論文（学術雑誌）, 共著, 査読有り

An Association with hypopituitarism and 9q subtelomere deletion syndrome.

Higuchi S, Takagi M, Takeda R, Yoshihashi H, Narumi S, Hasegawa T.

Clinical Case Reports 2018年

研究論文（学術雑誌）, 共著, 査読有り

Two novel mutations of COMP in Japanese boys with pseudoachondroplasia.

Ichihashi Y, Takagi M, Ishii T, Watanabe K, Nishimura G, Hasegawa T.

Hum Genome Variation 5 12 2018年

研究論文（学術雑誌）, 共著, 査読有り

A pediatric case of an insulinoma and a novel MEN1 mutation: the efficacy of the combination therapy of diazoxide and cornstarch.

Nakano S, Sato T, Hosokawa M, Takagi C, Yoshida F, Ishii T, Sato S, Hasegawa T.

Clin Pediatric Endocrinol 27 199 2018年

研究論文（学術雑誌）, 共著, 査読有り

Trismus-pseudocamptodactyly syndrome with bilateral hypoplastic mandibular condyles and shallow mandibular fossa: A case report.

Kusako C, Hori N, Izawa K, Kosaki R, Nishimura G, Hasegawa T.

Oral Science International 15 90-92 2018年

研究論文（学術雑誌）, 共著, 査読有り

Identification of a nonclassic TSH resistance patient with compound heterozygous TSHR mutations (p.[R109Q];[R450H]) and functional characterization of the mutant receptors.

Sugisawa C, Abe K, Sunaga Y, Taniyama M, Hasegawa T, Narumi S.

Clin Pediatr Endocrinol 27 123-130 2018年

研究論文（学術雑誌）, 共著, 査読有り

A pediatric case of pheochromocytoma without apparent hypertension associated with von Hippel-Lindau disease.

Igaki J, Nishi A, Sato T, Hasegawa T.

Clin Pediatr Endocrinol 27 87-93 2018年

研究論文（学術雑誌）, 共著, 査読有り

Longitudinal serum and urine steroid metabolite profiling in a 46,XY infant with prenatally identified POR deficiency.

Ono H, Numakura C, Homma K, Hasegawa T, Tsutsumi S, Kato F, Fujisawa Y, Fukami M, Ogata T.

J Steroid Biochem Mol Biol 178 177-184 2018年

研究論文（学術雑誌）, 共著, 査読有り

Serum 25-hydroxyvitamin D3 levels of one-month-old term infants in Tokyo using liquid chromatography tandem mass spectrometry.

Hara K, Koyama Y, Wada Y, Ikeda K, Hasegawa T.

Acta Paediatr 107 532-533 2018年

研究論文（学術雑誌）, 共著, 査読有り

Prevalence of central fatness in 1992-1994: 40% of Japanese boys 6-17 years.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T.

Endocrine J 65 213-220 2018年

研究論文（学術雑誌）, 共著, 査読有り

WHO 2006 Child Growth Standards overestimate short stature and underestimate overweight in Japanese children.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T.

J Pediatr Endocrinol Metab 26 33-38 2018年

研究論文（学術雑誌）, 共著, 査読有り

Association between monoallelic TSHR mutations and congenital hypothyroidism: a statistical approach.

Abe K, Narumi S, Suwanai AS, Adachi M, Muroya K, Asakura Y, Nagasaki K, Abe T, Hasegawa T.

Eur J Endocrinol 178 137-144 2018年

研究論文（学術雑誌）, 共著, 査読有り

A novel heterozygous intronic mutation in POU1F1 is associated with combined pituitary hormone deficiency.

Takagi M, Kamasaki H, Yagi H, Fukuzawa R, Narumi S, Hasegawa T.

Endocrine J 64 229-234 2017年

研究論文（学術雑誌）, 共著, 査読有り

Discordant fetal phenotype of hypophosphatasia in two siblings.

Ikenoue S, Miyakoshi K, Ishii T, Sato Y, Otani T, Akiba Y, Kasuga Y, Ochiai D, Matsumoto T, Matsuzaki Y, Tachikawa K, Michigami T, Nishimura G, Ikeda K, Hasegawa T, Tanaka M.

Am J Med Genet A 176 171-174 2017年

研究論文（学術雑誌）, 共著, 査読有り

Mild thyroid peroxidase deficiency caused by TPO mutations with residual activir: Correlation between clinical phenotypes and enzymatic activity.

Narumi S, Fox LA, Fukudome K, Sakaguchi Z, Sugisawa C, Abe K, Kameyama K, Hasegawa T.

Endocr J 64 1087-1097 2017年

研究論文（学術雑誌）, 共著, 査読有り

Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia.

Kizu R, Nishimura K, Sato R, Kosaki K, Tanaka T, Tanigawara Y, Hasegawa T.

Hor Res Peadiatr 88 316-323 2017年

研究論文（学術雑誌）, 共著, 査読有り

Incidence of diabetes mellitus and neoplasia in Japanese short-statured children treated with growth hormonr in the Genetics and neuroendocrinology of short stature international study (GeNeSIS)

Yokoya S, Hasegawa T, Ozono K, Tanaka H, Kanzaki S, Tanaka T, Chihara K, Jia N, Child CJ, Ihara K, Funai J, Iwamoto N, Seino Y.

Clin Pediatr Endocrinol 26 229-241 2017年

研究論文（学術雑誌）, 共著, 査読有り

Novel compound heterozygous mutations identiﬁed by whole exome sequencing in a Japanese patient with geroderma osteodysplastica.

Takeda R, Takagi M, Shinohara H, Futagawa H, Narumi S, Hasegawa T, Nishimura G, Yoshihashi H.

Eur J Med Genet 60 635-638 2017年

研究論文（学術雑誌）, 共著, 査読有り

A novel case of somatic KCNJ5 mutation in pediatric-onset aldosterone-producing adenoma.

Uchida N, Amano N, Yamaoka Y, Uematsu A, Sekine Y, Suzuki M, Watanabe J, Nishimoto K, Mukai K, Fukuzawa R, Hasegawa T, Ishii T.

J Endocrine Society 1 1056-1061 2017年

研究論文（学術雑誌）, 共著, 査読有り

Genetic defects in pediatric-onset adrenal insufficiency in Japan.

Amano N, Narumi S, Hayashi M, Takagi M, Imai K, Nakamura T, Hachiya R, Sasaki G, Homma K, Ishii T, Hasegawa T.

Eur J Endocrinol 177 187-194 2017年

研究論文（学術雑誌）, 共著, 査読有り

The response to growth hormone treatment in prepubertal children with growth hormone deficiency in Japan: Comparing three consecutive years of treatment data of The Foundation for Growth Science in Japan between the 1990s and 2000s.

Isojima T, Hasegawa T, Yokoya S, Tanaka T.

Endor J 30 851-858 2017年

研究論文（学術雑誌）, 共著, 査読有り

Homozygous DUOXA2 mutation (p.Tyr138*) in a girl with congenital hypothyroidism and her apparently unaffected brother: Case report and review of the literature.

Sugisawa C, Higuchi S, Takagi M, Hasegawa Y, Taniyama M, Abe K, Hasegawa T, Narumi S.

Endocr J 64 807-812 2017年

研究論文（学術雑誌）, 共著, 査読有り

Clinical practice guideline for congenital hyperinsulinism.

Yorifuji T, Horikawa R, Hasegawa T, Adachi M, Soneda S, Minagawa M, Ida S, Yonekura T, Kinoshita Y, Kanamori Y, Kitagawa M, Shinakai M, Sasaki H, Nio M.

Clin Pediatr Endocrinol 26 127-152 2017年

研究論文（学術雑誌）, 共著, 査読有り

Validation of auxological reference values for Japanese children with Noonan syndrome and comparison with growth in children with Turner syndrome.

Isojima T, Sakazume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T, Yokoya S.

Clin Pediatr Endocrinol 26 153-164 2017年

研究論文（学術雑誌）, 共著, 査読有り

Three-quarters adrenalectomy for infantile-onset Cushing syndrome due to bilateral adrenal hyperplasia in McCune-Albright syndrome.

Itonaga T, Goto H, Toujigamori M, Ohno Y, Korematsu S, TIzumi T, Narumi S, Hasegawa T, Ihara K.

Hor Res Paediatr 88 285-290 2017年

研究論文（学術雑誌）, 共著, 査読有り

yndromic disorder of sex development due to a novel hemizygous mutation in the carboxyl-terminal domain of ATRX.

Takagi M, Yagi H, Fukuzawa R, Narumi S, Hasegawa T.

Hum Genome Var 4 17012 2017年

研究論文（学術雑誌）, 共著, 査読有り

Shimada H. Severe hypertriglyceridemia during treatment of acute lymphoblastic leukemia associated with type III hyperlipoproteinemia

Yamada Y, Shima H, Shibata H, Ishii T, Hasegawa T,

Pediatr Blood Cancer 64 （ 11 ） 2017年

研究論文（学術雑誌）, 共著, 査読有り

FGFR1 Analyses in Four Patients with Hypogonadotropic Hypogonadism with Split-Hand/Foot Malformation: Implications for the Promoter Region.

Ohtaka K, Fujisawa Y, Takada F, Seo M, Kameda H, Hasegawa Y, Hasegawa T, Fukami M, Ogata T.

Hum Mutation 38 503-506 2017年

研究論文（学術雑誌）, 共著, 査読有り

Histological Change of Autoimmune Hepatitis with Graves’ disease; a child case report.

Yamada M, Shibata H, Masugi Y, Ishii T, Kameyama K, Ebinuma H, Hasegawa T.

Inter Med 56 2139-2143 2017年

研究論文（学術雑誌）, 共著, 査読有り

A novel mutation in the C-propeptide of COL2A1 causes atypical spondyloepiphyseal dysplasia cogenita.

Kusano C, Takagi M, Hori N, Murotsuki J, Nishimura G, Hasegawa T.

Hum Genome Var 4 17003 2017年

研究論文（学術雑誌）, 共著, 査読有り

A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency.

Takagi M, Dobashi K, Nagahara K, Kato M, Nishimura G, Fukuzawa R, Narumi S, Hasegawa T.

Am J Med Genet A 173 1071-1076 2017年

研究論文（学術雑誌）, 共著, 査読有り

Whole exome sequencing identified a novel COL2A1 mutation that causes mild spondylo-epiphyseal dysplasia mimicking autosomal dominat bracholmia.

Takagi M, Shimizu M, Suzuki E, Shinohara H, Narumi S, Hasegawa T, Nishimura G, Hasegawa Y.

Am J Med Genet 170 （ 3 ） 795 - 798 2016年03月

Waist-to-height ratio centiles by age and sex for Japanese children based on the 1978-1981 cross-sectional national survey data.

Inokuchi M, Matsuo N, Takayama J, Hasegawa T

Int J Obes (London) 40 65 - 70 2016年

共著

Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan Endocrine Society clinical practice guideline.

Yanase T, Tajima T, Katabami T, Iwasaki Y, Tanahashi Y, Sugawara A, Hasegawa T, Mune T, Oki Y, Nakagawa Y, Miyamura N, Shimizu C, Otsuki M, Nomura M, Akehi Y, Tanabe M, Kasayama S.

Endorine J 30 765 - 784 2016年

共著

Co-administration of the CYP3A4 inhibitor diltiazem counterscts the mitotane-induced clearance of glucocorticoids and antihypertensives in a patient with adrenocortical carcinoma.

Minami I, Yoshimoto T, Tsujimoto K, Homma K, Hasegawa T, Ogawa Y.

AACE Clin Case Reports 2 e36-e40 2016年

研究論文（学術雑誌）, 共著, 査読有り

Criteria for Radiological Diagnosis of Hypochondroplasia in Neonates.

Saito T, Nagasaki K, Nishimura G, Wada M, Nyuzuki H, Takagi M, Hasegawa T, Amano N, Murotsuki J, Sawai H, Yamada T, Sato S, Saitoh A.

Pediatr Radiol 46 513-518 2016年

研究論文（学術雑誌）, 共著, 査読有り

Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2.

Yoshizawa-Ogasawara A, Abe K, Ogikubo S, Narumi S, Hasegawa T, Satoh M.

J Pediatr Endocrinol Metab 29 363-371 2016年

研究論文（学術雑誌）, 共著, 査読有り

Growth references for Japanese individuals with Noonan syndrome.

Isojima T, Sakatsume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T, Yokoya S.

Pediatr Res 79 543-548 2016年

研究論文（学術雑誌）, 共著, 査読有り

A novel mutation of THRB Gene in a Japanese family with resistance to thyroid hormone.

Ito J, Narumi S, Nishizawa K, Kamimaki T, Hori N, Hasegawa T.

Clin Pediatr Endocrinol 25 19-22 2016年

研究論文（学術雑誌）, 共著, 査読有り

Classic and non-classic 21-hydroxylase deficiency can be discriminated from P450 oxidoreductase deficiency in Japanese infants by urinary steroid metabolites.

Koyama Y, Homma K, Fukami M, Miwa M, Ikeda K, Ogata T, Murata M, Hasegawa T.

Clin Pediatr Endocrinol 25 37-44 2016年

研究論文（学術雑誌）, 共著, 査読有り

Feminizing adrenocortical cartinoma with distinct histopathological findings.

Hatano M, Takenaka Y, Inoue I, Homma K, Hasegawa T, Sasano H, Awata T, Katayama S.

Intern Med 55 3301-3307 2016年

研究論文（学術雑誌）, 共著, 査読有り

Effects of financial support on treatment of adolescents with growth hormone deficiency: a retrospective study in Japan.

Maeda E, Higashi T, Hasegawa T, Yokoya S, Mochizuki T, Ishii T, Ito J, Kanzaki S, Shimatsu A, Takano K, Tajim T, Tanaka H, Tanahashi Y, Teramoto A, Nagai T, Hanew K, Horikawa R, Yorifuji T, Wada N, Tanaka T.

BMC Health Services Research 16 602 2016年

研究論文（学術雑誌）, 共著, 査読有り

A case of transient neonatal diabetes due to a novel mutation in ABCC8.

Takagi M, Takeda R, Yagi H, Ariyasu D, Fukuzawa R, Hasegawa T.

Clin Pediatr Endocrinol 25 139-141 2016年

研究論文（学術雑誌）, 共著, 査読有り

The distribution and cellular lineages of XX and XY cells in gonads associated with ovotesticular disorder of sexual development.

Nishina-Uchida N, Fukuzawa R, Ishii T, Anaka MR, Hasegawa T, Hasegawa Y.

Sex Dev. 10 185-190 2016年

研究論文（学術雑誌）, 共著, 査読有り

Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield Syndrome.

Takagi M, Miyoshi T, Nagashima Y, Shibata N, Yagi H, Fukuzawa R , Hasegawa T.

Hum Genome Var 3 16034 2016年

研究論文（学術雑誌）, 共著, 査読有り

Long-term clinical course in three patients with MAMLD1 mutations.

Fujisawa Y, Fukami M, Hasegawa T, Uematsu A, Koji M, Ogata T, Muroya K,

Endocrine J 63 835-839 2016年

研究論文（学術雑誌）, 共著, 査読有り

A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation.

Mitani M, Furuichi M, Narumi S, Hasegawa T, Chiga M, Uchida S, Sato S.

Clin Pediat Endocrinol 25 127-134 2016年

研究論文（学術雑誌）, 共著, 査読有り

A Novel dominant negative mutation in the intracellular domain of GHR is associated with growth hormone insensitivity.

Takagi M, Shinohara H, Nagashima Y, Hasegawa Y, Narumi S, Hasegawa T.

Clin Endocrinol 85 669-671 2016年

研究論文（学術雑誌）, 共著, 査読有り

Gonadal macrophage infiltration in congenital lipoid adrenal hyperplasia.

Ishii T, Fukuzawa R, Sato T, Muroya K, Adachi M, Ihara K, Igaki J, Hasegawa Y, Sato S, Mitsui T, Hasegawa T.

Eur J Endocrinol 175 127-132 2016年

研究論文（学術雑誌）, 共著, 査読有り

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M, Toyoshima K, Tanaka Y, Fukuzawa R, Miyako K, Kinjo S, Ohga S, Ihara K, Inoue H, Kinjo T, Hara T, Kohno M, Yamada S,Urano H, Kitagawa Y, Tsugawa K, Higa A, Miyawaki M, Okutani T, Kizaki Z, Hamada H, Kihara M, Shiga K, Yamaguchi T, Kenmochi M, Kitajima H, Fukami M, Shimizu A, Kudoh J, Shibata S, Okano H, Miyake N, Mastumoto N, Hasegawa T.

Nat Genet 48 792-797 2016年

研究論文（学術雑誌）, 共著, 査読有り

Potential utility of cinacalcet as a treatment for CDC73-1 related primary hyperparathyroidism: a case report.

Sato T, Muroya K, Hanakawa J, Yamashita S, Nozawa K, Masudo K, Yamanaka T, Asakura Y, Hasegawa T. Adachi M.

Clin Pediatr Endocrinol 25 91-98 2016年

研究論文（学術雑誌）, 共著, 査読有り

Stippled calcification in an infant with a recurrent SRCAP gene mutation.

Yagi H, Takagi M, Narumi S, Hasegawa T, Nishimura G, Hasegawa Y.

Am J Med Gent A 170 1088-1091 2016年

研究論文（学術雑誌）, 共著, 査読有り

Women with Turner syndrome are at high risk of lifestyle-related disease –From questionnaire surveys by the Foundation for Growth Science in Japan.

Hanew K, Tanaka T, Horikawa R, Hasegawa T, Fujita K, Yokoya S.

Endocrine J 63 449-456 2016年

研究論文（学術雑誌）, 共著, 査読有り

Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome.

Saito K, Matsuzaki T, Iwasa T, Miyado M, Saito H, Hasegawa T, Homma K, Inoue E, Miyashiro Y, Kubota T, Irahara M, Ogata T, Fukami M.

J Steroid Biochem Mol Biol 158 31-37 2016年

研究論文（学術雑誌）, 共著, 査読有り

A case of mature teratoma with a falsely high serum estradiol value measured with immunoassay.

Hosokawa M, Shibata H, Ishii T, Fujino A, Kuroda T, kosaki K, Kameyama K, Hasegawa T.

J Pediatr Endocrinol Metab 29 737-739 2016年

研究論文（学術雑誌）, 共著, 査読有り

A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes.

Takagi M, Takahashi M, Ohtsu Y, Sato T, Narumi S, Arakawa H, Hasegawa T.

Endocrine J 63 405-410 2016年

研究論文（学術雑誌）, 共著, 査読有り

Classic and non-classic 21-hydroxylase deficiency can be discriminated from P450 oxidoreductase deficiency in Japanese infants by urinary steroid metabolites.

Koyama Y, Homma K, Fukami M, Miwa M, Ikeda K, Ogata T, Murata M, Hasegawa T.

Clin Pediatr Endocrinol 25 37-44 2016年

研究論文（学術雑誌）, 共著, 査読有り

Criteria for Radiological Diagnosis of Hypochondroplasia in Neonates.

Saito T, Nagasaki K, Nishimura G, Wada M, Nyuzuki H, Takagi M, Hasegawa T, Amano N, Murotsuki J, Sawai H, Yamada T, Sato S, Saitoh A.

Pediatr Radiol 46 513-518 2016年

研究論文（学術雑誌）, 共著, 査読有り

Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2.

Yoshizawa-Ogasawara A, Abe K, Ogikubo S, Narumi S, Hasegawa T, Satoh M.

J Pediatr Endocrinol Metab 29 363-371 2016年

研究論文（学術雑誌）, 共著, 査読有り

Growth references for Japanese individuals with Noonan syndrome.

Isojima T, Sakatsume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T, Yokoya S.

Pediatr Res 79 543-548 2016年

研究論文（学術雑誌）, 共著, 査読有り

A novel mutation of THRB Gene in a Japanese family with resistance to thyroid hormone.

Ito J, Narumi S, Nishizawa K, Kamimaki T, Hori N, Hasegawa T.

Clin Pediatr Endocrinol 25 19-22 2016年

研究論文（学術雑誌）, 共著, 査読有り

Co-administration of the CYP3A4 inhibitor diltiazem counterscts the mitotane-induced clearance of glucocorticoids and antihypertensives in a patient with adrenocortical carcinoma.

Minami I, Yoshimoto T, Tsujimoto K, Homma K, Hasegawa T, Ogawa Y.

AACE Clin Case Reports 2 e36-e40 2016年

研究論文（学術雑誌）, 共著, 査読有り

The distribution and cellular lineages of XX and XY cells in gonads associated with ovotesticular disorder of sexual development.

Nishina-Uchida N, Fukuzawa R, Ishii T, Anaka MR, Hasegawa T, Hasegawa Y.

Sex Dev. 10 185-190 2016年

研究論文（学術雑誌）, 共著, 査読有り

Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield Syndrome.

Takagi M, Miyoshi T, Nagashima Y, Shibata N, Yagi H, Fukuzawa R , Hasegawa T.

Hum Genome Var 3 16034 2016年

研究論文（学術雑誌）, 共著, 査読有り

Long-term clinical course in three patients with MAMLD1 mutations.

Fujisawa Y, Fukami M, Hasegawa T, Uematsu A, Koji M, Ogata T, Muroya K,

Endocrine J 63 835-839 2016年

研究論文（学術雑誌）, 共著, 査読有り

A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation.

Mitani M, Furuichi M, Narumi S, Hasegawa T, Chiga M, Uchida S, Sato S.

Clin Pediat Endocrinol 25 127-134 2016年

研究論文（学術雑誌）, 共著, 査読有り

A Novel dominant negative mutation in the intracellular domain of GHR is associated with growth hormone insensitivity.

Takagi M, Shinohara H, Nagashima Y, Hasegawa Y, Narumi S, Hasegawa T.

Clin Endocrinol 85 669-671 2016年

研究論文（学術雑誌）, 共著, 査読有り

Gonadal macrophage infiltration in congenital lipoid adrenal hyperplasia.

Ishii T, Fukuzawa R, Sato T, Muroya K, Adachi M, Ihara K, Igaki J, Hasegawa Y, Sato S, Mitsui T, Hasegawa T.

Eur J Endocrinol 175 127-132 2016年

研究論文（学術雑誌）, 共著, 査読有り

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Nat Genet 48 792-797 2016年

研究論文（学術雑誌）, 共著, 査読有り

Potential utility of cinacalcet as a treatment for CDC73-1 related primary hyperparathyroidism: a case report.

Sato T, Muroya K, Hanakawa J, Yamashita S, Nozawa K, Masudo K, Yamanaka T, Asakura Y, Hasegawa T. Adachi M.

Clin Pediatr Endocrinol 25 91-98 2016年

研究論文（学術雑誌）, 共著, 査読有り

Stippled calcification in an infant with a recurrent SRCAP gene mutation.

Yagi H, Takagi M, Narumi S, Hasegawa T, Nishimura G, Hasegawa Y.

Am J Med Gent A 170 1088-1091 2016年

研究論文（学術雑誌）, 共著, 査読有り

Women with Turner syndrome are at high risk of lifestyle-related disease –From questionnaire surveys by the Foundation for Growth Science in Japan.

Hanew K, Tanaka T, Horikawa R, Hasegawa T, Fujita K, Yokoya S.

Endocrine J 63 449-456 2016年

研究論文（学術雑誌）, 共著, 査読有り

Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome.

Saito K, Matsuzaki T, Iwasa T, Miyado M, Saito H, Hasegawa T, Homma K, Inoue E, Miyashiro Y, Kubota T, Irahara M, Ogata T, Fukami M.

J Steroid Biochem Mol Biol 158 31-37 2016年

研究論文（学術雑誌）, 共著, 査読有り

A case of mature teratoma with a falsely high serum estradiol value measured with immunoassay.

Hosokawa M, Shibata H, Ishii T, Fujino A, Kuroda T, kosaki K, Kameyama K, Hasegawa T.

J Pediatr Endocrinol Metab 29 737-739 2016年

研究論文（学術雑誌）, 共著, 査読有り

A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes.

Takagi M, Takahashi M, Ohtsu Y, Sato T, Narumi S, Arakawa H, Hasegawa T.

Endocrine J 63 405-410 2016年

研究論文（学術雑誌）, 共著, 査読有り

Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan

Tanaka T, Igarashi Y, Ozono K, Ohyama K, Ogawa M, Osada H, Onigata K, Kanzaki S, Kohno H, Seino Y, Takahashi H, Tajima T, Tachibana K, Tanaka H, Nishi Y, Hasegawa T, Fujita K, Yorifuji T, Horikawa R, Yokoya S

Clin Pediatr Endocrinol 24 （ 4 ） 3167 - 3173 2015年10月

Growth references for Japanese individuals with Noonan syndrome.

Isojima T, Sakatsume S, Hasegawa T, Ogata T, Nakanishi T, Nagai T, Yokoya S

Pediatr Res in press 2015年

共著

TSH resistancerevisited.

Narumi S, Hasegawa T

Endocrine J 62 393 - 398 2015年

共著

原発性性腺機能低下症

長谷川奉延

小児内科増刊号　小児疾患診療のための病態生理２　改訂第5版（ in press ） 2015年

小児における内分泌機能検査の注意点

志村和浩、長谷川奉延

ホと臨床 in press 2015年

くり返す低血糖後にてんかんを発症した高インスリン血性低血糖症の1例

福間真実、宮井健太郎、高木優樹、後藤正博、鳴海覚志、長谷川奉延、長谷川行洋

小児科診療 78 139 - 141 2015年

Turenr症候群とCAHの合併を認めた副腎偶発腫の一例

岩橋泰幸、福岡秀規、中島進介、井口元三、本間桂子、長谷川奉延、小川渉、高橋裕

日本内分泌学会雑誌 91 （ Supple ） 44 - 46 2015年

Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2

Yoshizawa-Ogasawara A, Abe K, Ogikubo S, Narumi S, Hasegawa T, Satoh M

J Pediatr Endocrinol Metab in press 2015年

Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.

Clin Pediatr Endocrinol 24 3167 - 3173 2015年

A novel mutation of THRB Gene in a Japanese family with resistance to thyroid hormone.

Ito J, Narumi S, Nishizawa K, Kamimaki T, Hori N, Hasegawa T

Clin Pediatr Endocrinol in press 2015年

共著

Distinguishing from primary from secondary delta4-3-oxisteroid 5-reductase (SRD5B1, AKR1D1) deficiencyby urinary ateroid analysis.

Yanagi T, Mizuochi T, Homma K, Ueki I, Seki Y, Hasegawa T, Takei H, Nittono H, Kurosawa T, Matsuishi T, Kimura A

Clin Endocrinol 82 346 - 351 2015年

共著

Pseudodominant Inheritance in a Family with Non-autoimmune Hypothyroidism due to Biallelic DUOX2 Mutations.

Abe K, Narumi S, Suwanai AS, Hamajima T, Hasegawa T

Clin Endocrinol 83 394 - 398 2015年

共著

Elevated levels of plasma immunoassayable aldosterone in a mild form of 17-hydroxylaase/17,20-lyase deficiency diagnosed at the age of 50.

Ueda K, Usui T, Watanabe T, Kaneko K, Nakatani R, Kakita-Kobayashi M, Tanase-Nakao K, Nanba K, Tsuiki M, Tagami T, Naruse M, Toyoda Y, Homma K, Hasegawa T, Shimatsu A

AACE Clin Case Reports 1 e156 - e160 2015年

共著

Osteogenesis imperfecta IIC caused by a novel heterozygous mutation in the C-prppeptide region of COL1A1.

Takagi M, Matsushita M, Nishimura G, Hasegawa T

Human Genome Variation 1 14025 2015年

共著

Trends in thin body stature among Japanese female adolescents, 2003 to 2012.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T

Ann Hum Biol. 42 533 - 537 2015年

共著

Heterozygous defects in PAX6 gene and congenital hypopituitarism.

Takagi M, Nagasaki K, Fujiwara I, Ishii T, Amano N, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T

Eur J Endocrinol 172 37 - 45 2015年

共著

Waist Circumference centiles by age and sex for Japanese children based on the 1978-1981 cross-sectional national survey data.

Anzo M, Inokkuchi M, Matsuo N, Takayama JI, Hasegawa T

Ann Hum Biol 42 56 - 61 2015年

共著

Treatment of situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.

Sato N, Hasegawa T, Hasegawa Y, Arisaka O, Ozono K, Amemiya S, Kikuchi T, Tanaka H, Harada S, Miyata J, Tanaka T

Clin Pediatr Endocrinol 24 37 - 49 2015年

共著

Adult phenylketonuria presenting with subacute severe neurologic symptoms.

Seki M, Takizawa T, Suzuki S, Shimizu T, Shibata H, Ishii T, Hasegawa T, Suzuki N

J Clin Neuroscience 22 1361 - 1363 2015年

共著

A case with neonatal hyperinsulinemic hypoglycemia: It is a characteristic complication of Sotos syndrome.

Nakamura Y, Takagi M, Yoshihashi H, Miura M, Narumi S, Hasegawa T, Miyake Y, Hasegawa Y

Am J Med Genet 167A 1627 - 1631 2015年

共著

Severe osteogenesis imperfect caused by double substitutions of triple helical glycine residues in COL1A2.

Takagi M, Shinohara H, Narumi S, Nishimura G, Hasegawa Y, Hasegawa T

Am J Med Genet A 167 1627 - 1631 2015年

共著

A CYP3A4 inhibitor counterscts the mitotane-induced adrenal insufficiency and resistant hypertention in adrenocortical carcinoma.

Minami I, Yoshimoto T, Tsujimoto K, Homma K, Hasegawa T, Ogawa Y

AACE Clin Case Reports in press 2015年

共著

A novel mutation Ser344Cys in FGFR3 causes achondroplasia with severe platyspondyly.

Takagi M, Kouwaki M, Kawase K, Shinohara H, Hasegawa Y, Yamada T, Fujiwara I, Sawai H, Nishimura G, Hasegawa T

Am J Med Genet 167A 2851 - 2854 2015年

共著

Polyostotic osteolysis and hypophosphatemic rickets with elevated serum fibroblast growth factor 23: a case report.

Sato T, Muroya K, Asakura Y, Yachie A, Nishimura G, Aida N, Machida J, Tanaka Y, Hasegawa T, Adachi M

Am J Med Genet 167A 2430 - 2434 2015年

共著

Clinical manifestations and enzymatic activities of mitochondrial respiratory chain complexes in Pearson marrow-pancreas syndrome with 3-methylglutaconic aciduria: a case report and literature review.

Sato T, Muroya K, Hanakawa J, Asakura Y, Tanaka Y, Murayama K, Ohtake A, Hasegawa T, Adachi M

Eur J Pediatr 174 1593 - 1602 2015年

共著

Human chorionic gonadotropin stimulation test in prepubertal children with micropenis can accurately predict Leydig cell function in pubertal or postpubertal adolescents.

Ishii T. Matsuo N, Sato S, Ogata T, Tamai S, Anzo M, Kamimaki T, Sasaki G, Inokuchi M, Hori N, Amano N, Narumi S, Shibata H, Hasegawa T

Hor Res Paediatr 84 305 - 310 2015年

共著

Combined GH and TSH deficiency in a Japanese patient with a novel frameshift mutation in IGSF1.

Asakura Y, Abe K, Muroya K, Hanakawa J, Oto Y, Narumi S, Hasegawa T, Adachi M

Hor Res Pediatr 84 349 - 354 2015年

共著

小児における内分泌機能検査の注意点

志村和浩、長谷川奉延。　

ホルモンと臨床（医学の世界社） 62 （ 4 ） 341 - 343 2014年04月

共著

IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients.

Kato F, Hamajima T, Hasegawa T, Amano N, Horikawa R, Nishimura G, Nakashima S, Fuke T, Sano S, Fukami M, Ogata T.

Clin Endocrinol 80 706 - 713 2014年

共著

Steeper increases in body-mass index during childhood correlate with blood pressure elevation in adolescence: a long-term follow-up study in a Japanese community.

Kuwahara E, Asakura K, Nishiwaki Y, Komatsu H, Nakawaza A, Ushiku H, Maejima F, Nishigaki Y, Hasegawa T, Okamura T, Takebayashi T

Hypertension Res 37 179 - 184 2014年

共著

Neonatal case of classic maple syrup urine disease: Usefulness of 1H-MRS in early diagnosis.

Sato T, Muroya K, Hanakawa J, Asakura Y, Aida N, Tomiyasu M, Tajima G, Hasegawa T, Adachi M

Pediatr International 56 112 - 115 2014年

共著

A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation.

Takagi M, Narumi S, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T

Hor Res Paediatr 81 133 - 138 2014年

共著

Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study.

Miyake Y, Tanaka K, Nishikawa T, Naruse M, Takayanagi R, Sasano H, Takeda Y, Shibata H, Sone M, Satoh F, Yamada M, Ueshiba H, Katabami T, Iwasaki Y, Tanaka H, Tanahashi Y, Suzuki S, Hasegawa T, Katsumata N, Tajima T, Yanase T

Endocrine J 61 35 - 40 2014年

共著

Trends in thin body stature among Japanese male adolescents, 2003 to 2012.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T

Ann Hum Biol 41 277 - 281 2014年

共著

Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature.

Amano N, Mukai T, Iyo Y, Narumi S, Tanaka T, Yokoya S, Ogata T, Hasegawa T

J Clin Endocrinol Metab 99 E713 - F718 2014年

共著

A novel mutation in SOX3 polyalanine tract: A case of Kabuki syndrome with combined pituitary hormone deficiency harboring bouble mutations in MLL2 and SOX3.

Takagi M, Ishii T, Torii C, Kosaki K, Hasegawa T

Pituitary 17 569 - 574 2014年

共著

Two Japanese familial cases of Caffey disease with and without the common COL1A1 mutation and normal bone density, and review of the literature.

Kitaoka T, Miyoshi Y, Namba N, Miura K, Kubota T, Ohata Y, Fujiwara M, takagi M, Hasegawa T, Juppner H, Ozono K

Eur J Pediatr 173 799 - 804 2014年

共著

Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2

Mitsui T, Kim O-H, Hall C, Johnson D, Jin D-K, Toh T-H, Soneda S, Keino D, Matsubayashi S, Ishii T, Nishimura G, Hasegawa T

Am J Med Genet A 164A 2529 - 2534 2014年

共著

The contribution of serine 194 phosphorylation to steroidogenic acute regulatory protein function.

Sasaki G, Zubair M, Ishii T, Mitsui T, Hasegawa T, Auchus RJ

Mol Endocrinol 28 1088 - 1096 2014年

共著

Reference standard of penile size and prevalence of buried penis in Japanese newborn male infants.

Matsuo N, Ishii T, Takayama JI, Miwa M, Hasegawa T

Endocrine J 61 849 - 853 2014年

共著

Deletions in the 3’ part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

Schanze D, Neubauer D, Cormier-Daire V, Delrue MA, de Silva DC, Hasegawa T, Koenig R, Krueger G, Petit F, Schanze I, Seemanova E, Vogt J, Strom TM, Meinecke P, Reis A, Hennekam RCM, Zenker M

Hum Mutation 35 1092 - 1100 2014年

共著

Comprehensive Next Generation Sequencing Analyses of Hypoparathyroidism: Identification of Novel GCM2 Mutations.

Mitsui T, Narumi S, Inokuchi M, Nagasaki K, Nakazawa M, Sasaki G, Hasegawa T

J Clin Endocrinol Metab 99 E2421 - E2428 2014年

共著

Japanese founder duplication/triplications involving BHLHA) are associated with split-hand/foot malformation with or without long bone deficiency and Gallop-Wolfgang complex.

Nagata E, Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki H, Mizuno S, Watanabe S, Yoshiura K-i, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura N, Toda T, Takada S, Yokoyama S, Asahara H, Sano S, Fukami M, Ikegawa S, Ogata T

Orphanet J Rare Disease 9 125 2014年

共著

Effect of growth hormone treatment on quality of life in Japanese children with growth horomone deficiency: An analysis from a prospective observational study.

Tanaka T, Hasegawa T, Ozono K, Tanaka H, Kanzaki S, Yokoya S, Chihara K, Iwamoto N, Seino Y

Clin Pediatr Endocrinol 23 83 - 92 2014年

共著

Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: A patient report and review of the literature.

Adachi M, Muroya K, Asakura Y, Sugiyama K, Homma K, Hasegawa T

Horm Res Paediatr 82 138 - 142 2014年

共著

A novel KAL1 mutation is associated with combined pituitary hormone deficiency.

Takagi M, Narumi S, Hamada R, Hasegawa Y, Hasegawa T

Human Genome Variation 1 14011 2014年

共著

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation.

Asakura Y, Muroya K, Hanakawa J, Sato T, Aida N, Narumi S, Hasegawa T, Adachi M

Clin Pediatr Endocrinol 24 27 - 32 2014年

共著

Urinary steroid profiling: A powerful method for the diagnosis of abnormal steroidogenesis.

Koyama Y, Homma K, Hasegawa T

Exp Rev Endocrinol Metab 9 273 - 282 2014年

共著

A cross-sectional growth reference and chart of stretched penile length for Japanese boys aged 0-7 years.

Ishii T, Matsuo N, Inokuchi M, Hasegawa T

Hor Res Paediatr 82 388 - 393 2014年

共著

C-type natriuretic peptide (CNP) plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

Olney RC, Prickett TCR, Espiner EA, Mackenzie WG, Duker A, Ditro C, Zabel B, Hasegawa T, Kitoh H, Aylsworth AS, Bober MB

J Clin Endocrinol Metab 100 E355 - 359 2014年

共著

性分化疾患

林美恵、長谷川奉延

小児科診療 77増刊号「小児の治療指針」 602 - 603 2014年

Antley-Bixler症候群

細川真弓、長谷川奉延

日本臨床別冊「神経症候群Ⅳ－その他の神経疾患を含めて―（第2版）」　 489 - 491 2014年

肺炎球菌結合型ワクチンと子宮頸がん予防ワクチン

長谷川奉延、新庄正宜

メディカル・サイエンス・ダイジェスト 40 468 - 469 2014年

外陰部異常のみかた

佐々木悟郎、長谷川奉延

小児内科 46 859 - 863 2014年

性腺機能低下症

吉田理恵、長谷川奉延

内科 113 1599 - 1601 2014年

下垂体疾患のトランジション

安蔵慎、長谷川奉延

in press 2014年

成長ホルモン分泌不全性低身長症

上牧務、長谷川奉延

in press 2014年

未治療成人17α水酸化酵素欠損症患者の遺伝的、内分泌学的解析

201. 植田洋平、渡邊知一、臼井健、垣田真似子、中谷理恵子、中尾佳奈子、難波多拳、立木美香、田上哲也、成瀬光栄、金子恵一、本間桂子、長谷川奉延、島津章

日本内分泌学会雑誌 90 （ Suppl ） 72 - 74 2014年

周産期医療にかかわる全ての医師に御理解頂きたい新生児外陰部診察のコツ

長谷川奉延

日本周産期・新生児医学会雑誌 50 1198 - 1199 2014年

周産期医療にかかわる全ての医師に御理解頂きたい新生児外陰部診察のコツ

長谷川奉延

日本周産期・新生児医学会雑誌 50 1198 - 1199 2014年

遺伝子と性差

室谷浩二、長谷川奉延

日本臨床 73 686-692,2014 73 686 - 692 2014年

性分化疾患の基礎と臨床

長谷川奉延

日本生殖内分泌学会雑誌 19 5 - 9 2014年

IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients.

tKato F, Hamajima T, Hasegawa T, Amano N, Horikawa R, Nishimura G, Nakashima S, Fuke T, Sano S, Fukami M, Ogata T.

Clin Endocrinol 80 706 - 713 2014年

Steeper increases in body-mass index during childhood correlate with blood pressure elevation in adolescence: a long-term follow-up study in a Japanese community.

Kuwahara E, Asakura K, Nishiwaki Y, Komatsu H, Nakawaza A, Ushiku H, Maejima F, Nishigaki Y, Hasegawa T, Okamura T, Takebayashi T.

Hypertension Res 37 179 - 184 2014年

Neonatal case of classic maple syrup urine disease: Usefulness of 1H-MRS in early diagnosis.

Sato T, Muroya K, Hanakawa J, Asakura Y, Aida N, Tomiyasu M, Tajima G, Hasegawa T, Adachi M.

Pediatr Int 56 112 - 115 2014年

A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation.

Takagi M, Narumi S, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T.

Hor Res Paediatr 81 133 - 138 2014年

Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study.

Endocrine J 61 35 - 40 2014年

Trends in thin body stature among Japanese male adolescents, 2003 to 2012.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T.

Ann Hum Biol 41 277 - 281 2014年

Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature.

Amano N, Mukai T, Iyo Y, Narumi S, Tanaka T, Yokoya S, Ogata T, Hasegawa T.

J Clin Endocrinol Metab 99 E713 - F718 2014年

A novel mutation in SOX3 polyalanine tract: a case of Kabuki syndrome with combined pituitary hormone deficiency harboring bouble mutations in MLL2 and SOX3.

Takagi M, Ishii T, Torii C, Kosaki K, Hasegawa T.

Pituitary 17 569 - 574 2014年

Two Japanese familial cases of Caffey disease with and without the common COL1A1 mutation and normal bone density, and review of the literature.

Kitaoka T, Miyoshi Y, Namba N, Miura K, Kubota T, Ohata Y, Fujiwara M, takagi M, Hasegawa T, Juppner H, Ozono K.

Eur J Pediatr 173 799 - 804 2014年

Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2.

Mitsui T, Kim O-H, Hall C, Johnson D, Jin D-K, Toh T-H, Soneda S, Keino D, Matsubayashi S, Ishii T, Nishimura G, Hasegawa T.

Am J Med Genet A 164A 2529 - 2534 2014年

The contribution of serine 194 phosphorylation to steroidogenic acute regulatory protein function.

Sasaki G, Zubair M, Ishii T, Mitsui T, Hasegawa T, Auchus RJ.

Mol Endocrinol 28 1088 - 1096 2014年

Reference standard of penile size and prevalence of buried penis in Japanese newborn male infants.

Matsuo N, Ishii T, Takayama JI, Miwa M, Hasegawa T.

Endocrine J 61 849 - 853 2014年

Deletions in the 3’ part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

Schanze D, Neubauer D, Cormier-Daire V, Delrue MA, de Silva DC, Hasegawa T, Koenig R, Krueger G, Petit F, Schanze I, Seemanova E, Vogt J, Strom TM, Meinecke P, Reis A, Hennekam RCM, Zenker M.

Hum Mutation 35 1092 - 1100 2014年

Deletions in the 3’ part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

Schanze D, Neubauer D, Cormier-Daire V, Delrue MA, de Silva DC, Hasegawa T, Koenig R, Krueger G, Petit F, Schanze I, Seemanova E, Vogt J, Strom TM, Meinecke P, Reis A, Hennekam RCM, Zenker M.

Hum Mutation 35 1092 - 1100 2014年

Comprehensive Next Generation Sequencing Analyses of Hypoparathyroidism: Identification of Novel GCM2 Mutations.

Mitsui T, Narumi S, Inokuchi M, Nagasaki K, Nakazawa M, Sasaki G, Hasegawa T.

J Clin Endocrinol Metab 99 E2421 - E2428 2014年

Japanese founder duplication/triplications involving BHLHA9 are associated with split-hand/foot malformation with or without long bone deficiency and Gallop-Wolfgang complex.

Nagata E, Kano H, Kato F, Yamaguchi R, Nakashima S, Takayama S, Kosaki R, Tonoki H, Mizuno S, Watanabe S, Yoshiura K, Kosho T, Hasegawa T, Kimizuka M, Suzuki A, Shimizu K, Ohashi H, Haga N, Numabe H, Horii E, Nagai T, Yoshihashi H, Nishimura N, Toda T, Takada S, Yokoyama S, Asahara H, Sano S, Fukami M, Ikegawa S, Ogata T.

Orphanet J Rare Disease 9 125 - 125 2014年

Osteogenesis imperfecta IIC caused by a novel heterozygous mutation in the C-propeptide region of COL1A1.

Takagi M, Matsushita M, Nishimura G, Hasegawa T.

Human Genome Variation 1 （ 14025 ） 2014年

日齢７に感染を契機に副腎不全が増悪したX連鎖性先天性副腎低形成症の1例

1. 谷口裕子、門田行史、英雅世、醍醐政樹、嶋岡鋼、梅﨑光、田中吾朗、沼崎啓、福田冬季子、山形崇倫、天野直子、長谷川奉延、桃井真里子、郡司勇治

小児科臨床 66 247 - 252 2013年

Congenital hypothyroidism caused by a novel mutation of the dual oxidase2 (DUOX2) gene.

Yoshizawa-Ogasawara A, Ogikubo S, Satoh M, Narumi S, Hasegawa T

J Pediatr Endor Met 26 45 - 52 2013年

共著

Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment.

Seki Y, Mizuochi T, Kimura A, Takahashi T, Ohtake A, Hayashi S-i, Morimura T, Ohno Y, Hoshina T, Ihara K, Takei H, Nittono H, Kurosawa T, Homma K, Hasegawa T, Matsuishi T

J Inherit Metab Dis 36 565 - 573 2013年

共著

A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression.

Suwanai SA, Ishii T, Haruna H, Yamataka A, Narumi S, Fukuzawa R, Ogata T, Hasegawa T

Clin Endocrinol 78 957 - 965 2013年

共著

Reference intervals of urinary free adrenal steroids in Japanese newborn infants using stable isotope dilution - gas chromatography / mass spectrometry.

Koyama Y, Homma K, Miwa M, Ikeda K, Murata M, Hasegawa T

Clin Chem Acta 415 302 - 305 2013年

共著

Delayed onset congenital hypothyroidism in a patient with DUOX2 mutations and maternal iodine excess.

Kasahara T, Narumi S, Okasora K, Takaya R, Tamai H, Hasegawa T

Am J Med Genet A 161A 214 - 217 2013年

共著

Spousal choice by height in as urban middle-class Japanese

Uchida K, Matsuo N, Hori N, Hasegawa T, Takahashi T

Hum Biol 85 619 - 621 2013年

共著

Quantitative and Sensitive Detection of GNAS Mutations Causing McCune-Albright Syndrome with Next Generation Sequencing.

Narumi S, Matsuo K, Ishii T, Tanahashi Y, Hasegawa T

PLos One 8 e60525 2013年

共著

An observational study of the effectiveness and safety of growth hormone (HUmatrope) treatment in Japanese children with growth hormone deficiency or turner syndrome.

Tai S, Tanaka T, Hasegawa T, Ozono K, Tanaka H, Kanzaki S, Yokoya S, Fujieda K, Chihara K, Seino Y

Endcr J 60 57 - 64 2013年

共著

A homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency.

Yamaguchi R, Kato F, Hasegawa T, Katsumata N, Fukami M, Matsui T, Nagasaki K, Ogata T

Endcrine J 60 855 - 859 2013年

共著

Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome.

Fuke T, Mizuno S, Nagai T, Hasegawa T, Horikawa R, Miyoshi Y, Muroya K, Kondoh T, Numakura C, Sato S, Nakabayashi K, Tayama C, Hata K, Sano S, Matsubara K, Kagami M, Yamazawa K, Ogata T

PLos One 8 e60105 2013年

共著

A recurrent mutation in the 5’-UTR of IFITM5 causes osteogenesis imperfecta type V with broad phenotypic spectrum.

Takagi M, Sato S, Hara K, Tani C, Miyazaki O, Nishiura G, Hasegawa T

Am J Med Genet A 161A 1980 - 1982 2013年

共著

Novel compound heterozygous mutations of the growth horomone-releasing hormone receptor gene in a case of isolated growth hormone deficiency.

Soneda A, Adachi M, Muroya K, Asakura Y, Takagi M, Hasegawa T, Inoue H, Itakura M

GH IGF Res 23 89 - 97 2013年

共著

Association between Graves’ Disease and Renal Coloboma Syndrome: a case.

Sato T, Muroya K, Hanakawa J, Asakura Y, Takahashi E, Shiroyanagi Y, Yamazaki Y, Tanaka Y, Hasegawa T, Adachi M

Clin Pediatr Endocrinol 22 45 - 51 2013年

単著

Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.

Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, Takada F, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T, Nakayama K, Inoue S-i, Watanabe K, Ogura T, Matsubara Y

Am J Hum Genet 93 173 - 180 2013年

共著

A 2.0 Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum.

Takagi M, Sasaki G, Mitsui T, Honda M, Tanaka Y, Hasegawa T

Eur J Med Genet 56 526 - 528 2013年

共著

Heterozygous mutations in natriuretic peptide receptor-B gene (NPR2) as a cause of idiopathis short stature.

Vasques GA, Naoko A, Quedas EPS, Docko AJ, Funari MF, Nishi MY, Arnhold IJP, Hasegawa T, Jorge AA

J Clin Endocrinol Metat 98 E1636 - 1644 2013年

共著

Characteristic testicular histology is useful for the identification of NR5A1 gene mutation in prepubertal 46,XY patients.

Nishina-Uchida N, Fukuzawa R, Numakura C, Suwanai A, Hasegawa T, Hasegawa Y

Hor Res Paediatr 80 119 - 128 2013年

共著

Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1. Endocrine J 60:51-55,2013.

Kondo E, Nakamura A, Homma K, Hasegawa T, Yamaguchi T, Narugami T, Aoyagi H, Ishizu K, Tajima T

Endocrine J 60 51 - 55 2013年

共著

Pseudopseudohypoparathyroidism with a novel mutation in the GNAS gene showing thin bones of extremities and ossification of enthuses.

Hamasaki H, Mukaino T, Kaneko H, Mitsui T, Moriyama S, Hasegawa T, Yanai H

J Endocrinol Metab 3 150 - 152 2013年

共著

A 68-year-old phenotypically male patient with 21-hydroxylase deficiency and concomitant adrenocortical neoplasm producing testosterone and cortisol.

Hayashi M, Kataoka Y, Sugimura Y, Kato F, Fukami M, Ogata T, Homma K, Hasegawa T, Oiso Y, Sasano H, Tanaka H

Tohoku J Exp Med 231 75 - 84 2013年

共著

Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development.

Fukami M, Homma K, Hasegawa T, Ogata T

Dev Dynamics 242 320 - 329 2013年

共著

尿ステロイドプロフィルによる新生児副腎皮質疾患の早期診断

本間桂子、長谷川奉延

小児科臨床 66 199 - 207 2013年

182. 鳴海覚志、長谷川奉延。　次世代シークエンサーによる先天性内分泌疾患の分子基盤の解明　医学のあゆみ　　245 427-432 (2013) 次世代シークエンサーによる先天性内分泌疾患の分子基盤の解明

鳴海覚志、長谷川奉延

医学のあゆみ 245 427 - 432 2013年

クラインフェルター症候群

長谷川奉延

分子精神医学 13 220 - 221 2013年

副腎皮質系機能検査の進め方

柴田浩憲、長谷川奉延

小児内科 45 827 - 831 2013年

高カリウム血症副腎不全

吉田理恵、長谷川奉延

小児内科 45 1603 - 1606 2013年

急性化膿性甲状腺炎・亜急性甲状腺炎・無痛性甲状腺炎

土岐真智子、上野滋、長谷川奉延

小児科 54 1213 - 1219 2013年

甲状腺疾患に対する遺伝子検査

鳴海覚志、長谷川奉延

小児科 54 1105 - 1112 2013年

先天性甲状腺機能低下症の遺伝子診断

鳴海覚志、長谷川奉延

ホと臨床 61 67 - 74 2013年

小児肥満症に対する集学的治療

井ノ口美香子、長谷川奉延

ホと臨床 61 177 - 182 2013年

内分泌疾患－成人と小児で成因・病態・診断・治療・合併症・予後は同じか－

長谷川奉延

ホと臨床 61 335 - 336 2013年

17OHP

小山雄平、長谷川奉延

ホと臨床 61 467 - 471 2013年

エピジェネティクス：内分泌科医が理解すべき遺伝学の新しい視点

長谷川奉延

ホと臨床 61 591 - 592 2013年

偽性副甲状腺機能低下症：GNAS遺伝子とインプリンティング

三井俊賢、長谷川奉延

ホと臨床 61 653 - 658 2013年

生殖補助医療、性ホルモン補充を行わず、妊娠・出産に至った先天性リポイド副腎過形成の1例

磯部まり子、市川義一、池ノ内学、山田卓博、根本泰子、服部政博、住友直文、西澤和倫、長谷川奉延

静岡産婦人科学会雑誌 2 38 - 43 2013年

8歳で診断された甲状腺ペルオキシダーゼ（TPO）遺伝子異常による甲状腺腫性クレチン症の女児例

福留啓祐、坂口善市、阿部容子、木下ゆき子、市原朋子、藤井笑子、関口隆憲、大原克明、鳴海覚志、阿部清美、長谷川奉延

高松赤十字病院紀要 1 4 - 44 2013年

日本人の成長ホルモン分泌不全性低身長症における成長ホルモン治療　ノルディトロピン®製造販売後調査（NordiPAD®）からの中間報告―脂質代謝に対する影響を中心に―　45 2061-2068,2013

田島敏広、安達昌功、大薗恵一、田中敏章、長谷川奉延、堀川玲子、横谷進、冨田美香

ノルディトロピン®製造販売後調査（NordiPAD®）からの中間報告―脂質代謝に対する影響を中心に― 45 2061 - 2068 2013年

被虐待児症候群と鑑別が困難であった骨系統疾患の2例

今嶋由香理、北野元裕、上田孝文、岡本伸彦、髙木優樹、長谷川奉延

近畿小児整形外科 25 33 - 36 2012年

Atypical Achondroplasia due to Somatic Mosaicism for the Common Thanatophoric Dysplasia Mutation R248C.

Takagi M, Kaneko-Schmitt S, Suzumori N, Nishimura G, Hasegawa T

Am J Med Genet A 158A 247 - 250 2012年

共著

Radiological clues to the early diagnosis of hypochondroplasia in the neonatal period: Report of two patients.

Saito T, Nagasaki K, Nishimura G, Takagi M, Hasegawa T, Uchiyama M

Am J Med Genet 158A 630 - 634 2012年

共著

A family of pseudohypoparathyroidism type Ia with an 850-kb submicroscopic deletion encompassing the whole GNAS locus.

Mitsui T, Nagasaki K, Takagi M, Narumi S, Ishii T, Hasegawa T

Am J Med Genet A 158A 261 - 264 2012年

共著

Two-step biochemical differential diagnosis of classical 21-hydroxylase deficiency and cytochrome P450 oxidoreductase deficiency in Japanese infants using urinary pregnanetriolone/tetrahydroxycortisone ratio and 11-hydroxyandrosterone by gas...

Koyama Y, Homma K, Fukami M, Miwa M, Ikeda K, Ogata T, Hasegawa T, Murata M

Clin Chem 58 741 - 747 2012年

共著

Mosaic upd(7)mat in a patient with Silver-Russell syndrome.

Fuke-Sato T, Yamazawa K, Nakabayashi K, Matsubara K, Matsuoka K, Hasegawa T, Dobashi K, Ogata T

Am J Med Genet 158A 465 - 468 2012年

共著

A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney.

Abe Y, Sato T, Takagi M, Watanabe T, Nagayama Y, Hasegawa T, Abe T

J Pediatr Endocr Met 25 587 - 590 2012年

共著

Favorable impact on growth hormone treatment on cholesterol levels in Turner syndrome.

Kohno H, Igarashi Y, Ozono K, Ohyama K, Ogawa M, Osada H, Onigata K, Kanzaki S, Seino Y, Takahashi H, Tajima T, Tachibana K, Tanaka H, Nishi Y, Hasegawa T, Fujieda K, Fujita K, Horikawa R, Yokoya S, Yorifuji T, Tanaka T

Clin Pediatr Endocrinol 21 29 - 34 2012年

共著

A genome-wide expression profile of adrenocortical cells in knockout mice lacking steroidogenic acute regulatory protein.

Ishii T, Mitsui T, Suzuki S, Matsuzaki Y, Hasegawa T

Endocrinol 153 2714 - 2723 2012年

共著

A novel mutation in LEPRE1 that eliminates only the KDEL ER- retrieval sequence causes non-lethal osteogenesis imperfect.

Takagi M, Ishii T, Barnes AM, Weis MA, Amano N, Tanaka M, Fukuzawa R, Nishimura G, Eyre DR, Marini JC, Hasegawa T

PLos One 7 e36809 2012年

共著

Prenatal diagnosis of osteogenesis imperfecta type II by three-dimensional computed tomography (CT): the current state of fetal CT.

Akizawa Y, Nishimura G, Hasegawa T, Takagi M, Kawamichi Y, Matsuda Y, Matsui H, Saito K

Cong Anomalies(Kyoto) 52 203 - 206 2012年

共著

Hypoglycemia associated with L-asparaginase in acute lymphoblastic leukemia treatment: a case report.

Tanaka R, Osumi T, MiharuM, Ishii T, Hasegawa T, Takahashi T, Shimada H

Exp Hematol Oncol 1 8 2012年

共著

PAPSS2 mutations cause autosomal recessive brachyolmia.

Miyake N, Elcioglu NH, Iida A, Isguven P, Dai J, Murakami N, Takamura K, Cho T-J, Kim O-H, Hasegawa T, Nagai T, Ohashi H, Nishimura G, Matsumoto N, Ikegawa S

J Med Genet 49 533 - 538 2012年

共著

Recurrence of osteogenesis imperfect due to maternal mosaicism of a novel COL1A1 mutation.

Yamada T, Takagi M, Nishimura G, Akaishi R, Furuta I, Morikawa M, Yamada T, Cho K, Sawai H, Ikegawa S, Hasegawa T, Minakami H

Am J Med Genet A 158A 2969 - 2971 2012年

共著

Functional characterization of four novel PAX 8 mutations causing congenital hypothyroidism: New evidence for haploinsufficiency as a a disease mechanism.

Narumi S, Araki S, Hori N, Muroya K, Yamamoto Y, Asakura Y, Adachi M, Hasegawa T

Eur J Endocrinol 167 625 - 632 2012年

共著

Gradual loss of ACTH due to a novel mutation in LHX4: Comprehensive mutation screening in Japanese patients with congenital hypopituitarism.

Takagi M, Ishii T, Inokuchi M, Amano N, Asakura Y, Muroya K, Hasegawa Y, Adachi M, Hasegawa T

PLos One 7 e46008 2012年

共著

成長曲線を正しく使おう―身長・体重・頭囲・座高・腹囲・伸展陰茎長・精巣容積・BMI―

井ノ口美香子、長谷川奉延

小児科診療 75 353 - 361 2012年

内分泌器官の器官形成とその異常

鳴海覚志、長谷川奉延

小児科診療 75 483 - 489 2012年

ホルモンが関係する病気

長谷川奉延

からだの科学 272 98 - 101 2012年

子どものホルモンの病気をご存じですか？

長谷川奉延

塾 273 25 2012年

なぜ今、日常診療に小児内分泌学か？

長谷川奉延

小児科診療 75 9 2012年

副腎皮質機能低下症のアルゴリズム

天野直子、長谷川奉延

小児内科 44 588 - 592 2012年

マッキュン・オルブライト症候群

堀尚明、長谷川奉延

内科 109 1312 - 1313 2012年

先天性副腎ステロイド産生異常症の最近の話題

長谷川奉延

最新医学 67 1989 - 1995 2012年

小児科領域から見た小児の成長障害

有安大典、長谷川奉延

臨床整形外科 47 1202 - 1206 2012年

グルココルチコイド反応性アルドステロン症(GRA)

林美恵、長谷川奉延

ホと臨床 60 189 - 192 2012年

先天性副腎皮質過形成症

佐藤武志、長谷川奉延

ホと臨床 60 227 - 231 2012年

小児慢性疾患の生活指導（思春期早発症および遅発症、ターナー症候群）

佐々木悟郎、長谷川奉延

小児科臨床 65 727 - 733 2012年

機能低下型TSH受容体変異

鳴海覚志、長谷川奉延

ホと臨床 60 501 - 506 2012年

FGFR3異常症

髙木優樹、長谷川奉延

ホと臨床 60 535 - 541 2012年

小児内分泌疾患の診断と治療　－日本と世界は何が同じで何が違うのか－

長谷川奉延

ホと臨床 60 667 2012年

先天性副腎皮質過形成

天野直子、長谷川奉延

小児内科 44増刊号 2210 - 2211 2012年

RSウイルス感染症とインフルエンザウイルス感染症について

長谷川奉延、新庄正宜

クリニシアン 59 782 - 784 2012年

ホルモン受容体異常症を通してホルモンと受容体の機能を再整理・理解しよう

長谷川奉延

ホと臨床 60 （ 495 ） 495 - 496 2012年

新生児マス・スクリーニング検査の17α水酸化プロゲステロン（17-OHP）高値を契機に、内分泌学的検査をもとに診断されたACTH非依存性Cushing症候群の1例

12. 橘田一輝、田久保憲行、昆信也、大津成之、風張眞由美、横田行史、笹野公伸、本間桂子、長谷川奉延、石井正浩

日本マス・スクリーニング学会誌 22 212 - 216 2012年

GNAS変異陰性ー偽性副甲状腺機能低下症IaにおけるGNAS遺伝子領域の全てを含む欠失の同定

三井俊賢、長崎啓祐、高木優樹、鳴海覚志、石井智弘、長谷川奉延

ホルモンと臨床 201 （ 59 ） 1085-1087 2011年12月

研究論文（学術雑誌）, 共著

A neonatal onset succinyl-CoA:3-ketoacid CoA transferase (SCOT)-deficient patient with T435N and c.658-666dupAACGTGATT p.N220_I222dup mutations in the OXCT1 gene.

長谷川奉延

J Inherit Metab Dis 33 （ Suppl 3 ） S307 - S313 2011年12月

研究論文（学術雑誌）, 共著

グルコキナーゼ遺伝子新規変異による先天性インスリン過剰症の一家族例

七尾謙治、依藤亨、上牧務、勝丸雅子、高橋亨岳、志賀健太郎、姜知佳、井上達秀、長谷川奉延

ホルモンと臨床 201 （ 59 ） 1049-1051 2011年12月

研究論文（学術雑誌）, 共著

Heterozygous C-propeptide mutations in COL1A1: Osteogenesis imperfect type IIC and dense bone variant.

長谷川奉延

Am J Med Genet 155A （ 9 ） 2269 - 2273 2011年09月

研究論文（学術雑誌）, 共著

Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake.

長谷川奉延

J Clin Endocrinol Metab 96 （ 8 ） E1340 - E1345 2011年08月

研究論文（学術雑誌）, 共著

Syndrome of inappropriate anti-diuretic hormone in Kawasaki disease.

長谷川奉延

Pediatr International 53 （ 3 ） 354 - 357 2011年06月

研究論文（学術雑誌）, 共著

内臓肥満評価におけるBMIの位置づけ―日本人肥満小児におけるBMIと内臓脂肪量・肥満合併症との関係―

井ノ口美香子、荒木俊介、土橋一重、朝山光太郎、長谷川奉延、徳村光昭、南里清一郎

慶應保健研究 29 25 - 29 2011年

Tracking of BMI in Japanese children from 6 to 18 years of age: Reference values for annual BMI incremental change and proposal for size of increment indicative of risk for obesity

長谷川奉延

Ann Hum Biol 38 146-149 2011年

研究論文（学術雑誌）, 共著

Medical professionalism教育の一環としての白衣式における誓いの言葉プロジェクト

戸谷遼、奥山訓子、神山圭介、安井哲也、長谷川奉延、平形道人、渡辺賢治

医学教育 42 （ 5 ） 283-287 2011年

研究論文（学術雑誌）, 共著

Prenatal diagnosis of osteogenesis imperfect type II by three-dimensional ultrasound and computed tomography.

Suzumori N, Hasegawa T, Sugiura-Ogasawara M

J Obstet Gynaecol Res 37 664 - 665 2011年

共著

Molecular Basis of Thyroid Dyshormonogenesis: Genetic Screening in Population-Based Japanese Patients.

Narumi S, Muroya K, Asakura Y, Adachi M, Hasegawa T

J Clin Endicrinol Metab 96 E1838 - 1842 2011年

共著

BMI z-score is the optimal measure of annual adiposity change in elementary children.

Inokuchi M, Matsuo N, Takayama JI, Hasegawa T

Ann Hum Biol 38 747 - 751 2011年

共著

PAX8 mutation disturbing thyroid follicular growth: A case report.

Narumi S, Yoshida A, Muroya K, Asakura Y, Adachi M, Fukuzawa R, Kameyama K, Hasegawa T

J Clin Endocrinol Metab 96 E2039 - 2044 2011年

共著

Free cortisol/cortisone ration in pooled urine was increased after rapid-ACTH stimulation test under dexamethasone suppression.

Koyama Y, Homma K, Murata M, Shibata H, Itoh H, Hasegawa T

Endocrine J 58 1099 - 1103 2011年

共著

先天性甲状腺機能低下症の遺伝子診断

鳴海覚志、長谷川奉延

ホと臨床 59 565 - 572 2011年

先天性副腎皮質過形成症

細川真弓、長谷川奉延

ホと臨床 59 1001 - 1006 2011年

軽症あるいは軽度小児内分泌疾患の定義と治療適応・治療戦略をどう考えるか

長谷川奉延

ホと臨床 59 863 - 864 2011年

非古典型副腎過形成症

天野直子、長谷川奉延

ホと臨床 59 875 - 879 2011年

。高用量GH治療によりターナー症候運の治療効果：ターナー症候群GH治療共同研究（TRC）の7年間の治療経験

9. 田中敏章、五十嵐裕、大薗恵一、大山健司、小川正道、長田久雄、鬼形和道、神崎晋、河野斉、清野佳紀、高橋弘昭、田島敏広、立花克彦、田中弘之、西美和、長谷川奉延、藤枝憲二、藤田敬之助、堀川玲子、横谷進、依藤亨

日本成長学会雑誌 17 9 - 15 2011年

Medical professionalism教育の一環としての白衣式における誓いの言葉プロジェクト

戸谷遼、奥山訓子、神山圭介、安井哲也、長谷川奉延、平形道人、渡辺賢治

医学教育 42 283 - 287 2011年

成長ホルモン分泌不全性低身長症における成長ホルモン前思春期の治療開始年齢別治療効果

8. 田中敏章、伊藤純子、神崎晋、島津章、田中弘之、寺本明、永井敏郎、長谷川奉延、羽二生邦彦、藤田敬之助、堀川玲子、向井徳男、和田尚弘、横谷進

日本成長学会雑誌 16 23 - 29 2010年

アンドロゲン不応症

天野直子、長谷川奉延

産科と婦人科 77 1283 - 1287 2010年

家族性先天性甲状腺機能低下症の臨床的・分子遺伝学的検討

長崎啓祐、鳴海覚志、浅見直、小川洋平、菊池透、長谷川奉延、内山聖

ホと臨床 57 1001 - 1005 2010年

尿中遊離型ベタメサゾンGC/MS測定法の確立と母体投与早産児尿中遊離型ベタメサゾン分析　ホと臨床 57 1013-1015 (2010)

小山雄平、本間桂子、三輪雅之、丹羽房子、河井昌彦、村田満、池田一成、長谷川奉延

ホと臨床 57 1013 - 1015 2010年

日本における21-水酸化酵素欠損症の出生前診断・治療の現状調査

田島敏広、長谷川奉延、小川英伸、堀川玲子、木下英一、原田正平、猪股弘明、安達昌功、西美和、楠田聡、大関武彦、藤枝憲二

ホと臨床 57 1021 - 1023 2010年

SF-1, DAX-1と小児内分泌疾患

佐々木悟郎、長谷川奉延

ホと臨床 58 157 - 162 2010年

性分化異常症

林美恵、長谷川奉延

小児科診療 73 563 - 564 2010年

中枢性尿崩症

本田美紗、長谷川奉延

小児内科増刊号 42 664 - 666 2010年

副腎疾患と成長障害

諏訪内亜由子、長谷川奉延

小児内科 42 571 - 577 2010年

非古典型21水酸化酵素欠損症の治療は必要か？

高木優樹、長谷川奉延

ホと臨床 58 335 - 339 2010年

骨形成不全症

高木優樹、長谷川奉延

ホと臨床 58 587 - 593 2010年

先天性甲状腺機能低下症の分子遺伝学

鳴海覚志、長谷川奉延

ホと臨床 58 565 - 571 2010年

遺伝子レベルよりみた性差

天野直子、長谷川奉延

診断と治療 98 1087 - 1092 2010年

中枢性尿崩症

本田美紗、長谷川奉延

小児内科 42 664 - 666 2010年

アンドロゲン不応症

天野直子、長谷川奉延

産科と婦人科 77 1283-1287 (2010) 77 1283 - 1287 2010年

非古典型21水酸化酵素欠損症の治療は必要か?

高木優樹、長谷川奉延

ホと臨床 58 335 - 339 2010年

思春期における性分化疾患の治療とカウンセリング

天野直子、長谷川奉延

産婦人科の実際 59 447 - 452 2010年

Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: Identification of a7.2-kb microdeletion using oligonucleotide tiling microarray

長谷川奉延

Am J Med Genet 152A 133-140 2010年

研究論文（学術雑誌）, 共著

The effect of intramuscular testosterone enanthate treatment on stretched penile length in prepubertal boys with hypospadias

長谷川奉延

J Urol 76 97-100 2010年

研究論文（学術雑誌）, 共著

Transcription-factor mutations and congenital hypothyroidism: Systematic genetic screening of a population-based cohort of Japanese patients

長谷川奉延

J Clin Endocrinol Metab 95 1981-1985 2010年

研究論文（学術雑誌）, 共著

Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing’s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome

長谷川奉延

Endocrine J 57 819-824 2010年

研究論文（学術雑誌）, 共著

Progression of Goiter in Pendred Syndrome is Associated with Increase of Thyroidal Iodine Uptake but not with Iodine Organification Defect: Report of a Patient with SLC26A4 Mutations

長谷川奉延

Am J Med Genet 152A 1793-1997 2010年

研究論文（学術雑誌）, 共著

One novel and two recurrent THRB mutations associated with resistance to thyroid hormone: Structure-based computational mutation prediction

長谷川奉延

Clin pediatr Endocrinolo 19 91-99 2010年

研究論文（学術雑誌）, 共著

Ruvalcaba syndrome revisited

長谷川奉延

Am J Med Genet 152A 1854-1857 2010年

研究論文（学術雑誌）, 共著

Late manifestations of Tricho-Rhino-Pharangeal syndrome in a patient: Expanded skeletal phenotype in adulthood

長谷川奉延

Am J Med Genet 152(A) 2115-2119 2010年

研究論文（学術雑誌）, 共著

小児期メタボリックシンドロームの早期診断とその意義

井ノ口美香子、長谷川奉延

小児科診療 73 277 - 282 2010年

胎児骨形成不全II型の一例　東海産婦人科学会雑誌 46:121-125,2009.

大林伸太郎、鈴森伸宏、水谷栄太、服部幸雄、北折珠央、金子さおり、鈴木佳克、高木優樹、長谷川奉延、杉浦真弓

東海産婦人科学会雑誌 46 121 - 125 2009年

低ゴナドトロピン性性腺機能低下症の成因と治療

長谷川奉延

小児科臨床 62 1779 - 1784 2009年

小児のアンドロゲン

佐々木悟郎、石井智弘、本間桂子、長谷川奉延

臨床泌尿器科 63 117 - 121 2009年

小児における副腎ホルモン補充療法の現状と展望

林美恵、長谷川奉延

ホと臨床 57 905 - 908 2009年

性分化異常症発症責任遺伝子MAMALD1の臨床的および分子遺伝学的解析

深見真紀、和田友香、上松あゆ美、長谷川奉延、緒方勤

ホと臨床 57 1025 - 1029 2009年

小児期発症バセドウ病薬物治療のガイドライン

4. 佐藤浩一、佐々木望、原田正平、田中敏章、赤須文人、朝山光太郎、荒田尚子、猪股弘明、大江秀美、鬼形和道、神崎晋、杉原茂孝、田尻淳一、田中弘之、西山宗六、長谷川奉延、長谷川行洋、深田修司、百渓尚子、横谷進、吉村弘、森昌朋、藤枝憲二

日児誌 112 946 - 952 2008年

SF-1 mutation in human.

Hasegawa T

GGH 24 1 - 5 2008年

単著

内分泌疾患診療の進歩と展望

長谷川奉延

小児科診療 71 2001 - 2006 2008年

小児成長障害における本邦のGH治療の現状

上牧務、長谷川奉延

内分泌・糖尿病科 26 419 - 424 2008年

軟骨無形成症、軟骨低形成症

上牧務、長谷川奉延

小児内科 40 1797 - 1800 2008年

低ゴナドトロピン性性腺機能低下症・思春期早発症とGPR54

髙木優樹、長谷川奉延

ホと臨床 56 779 - 786 2008年

小児のCushing症候群の診断と問題点

天野直子、長谷川奉延

ホと臨床 56 1107 - 1111 2008年

先天性甲状腺機能低下症におけるTSH不応症の臨床的および遺伝学的検討

長崎啓祐、鳴海覚志、浅見直、菊池透、長谷川奉延、内山聖

ホと臨床 56 1213 - 1216 2008年

SGA児とAGA児における成長ホルモン長期治療効果の比較

田中敏章、伊藤純子、島津章、田中弘之、寺本明、永井敏郎、長谷川奉延、羽二生邦彦、藤田敬之助、堀川玲子、向井徳男、和田尚弘、横谷進

ホと臨床 56 1199 - 1202 2008年

性分化異常

佐々木悟郎、長秀男、長谷川奉延

小児内科 40増刊号 786 - 792 2008年

HDR症候群16家系29例の臨床分子遺伝学的解析転写因子GATA3腎尿路系発生における役割についての考察

室谷浩二、安達昌功、山中美智子、田中美緒、田中祐吉、長谷川奉延、緒方勤

発達腎研究会誌 16 29 - 35 2008年

年齢別およびSGA児とAGA児における成長ホルモン治療の1年目の効果の比較

田中敏章、伊藤純子、島津章、田中弘之、寺本明、永井敏郎、長谷川奉延、羽二生邦彦、藤田敬之助、堀川玲子、向井徳男、和田尚弘、横谷進

日本成長学会雑誌 14 25 - 30 2008年

ターナー症候群におけるエストロゲン補充療法ガイドライン　日児誌 112:1048-1050,2008.

田中敏章、横谷進、長谷川奉延、神崎晋、杉原茂孝、田中弘之、原田正平、藤枝憲二

日児誌 112 1048 - 1050 2008年

成長・成熟の異常　やせ

井ノ口美香子、長谷川奉延

小児科診療増刊号 235 - 237 2007年

肥満

井ノ口美香子、長谷川奉延

小児科 48 662 - 666 2007年

成長障害から発見されたCushing症候群

井ノ口美香子、長谷川奉延

小児内科 39 742 - 744 2007年

下垂体・視床下部性性腺機能不全―hCG, hMG/rhFSH療法

堀尚明、長谷川奉延

小児内科 39 948 - 949 2007年

著しい身長増加に気づかれながら3年間診断されなかった甲状腺機能亢進症の1例

柳忠宏、井ノ口美香子、堀尚明、長谷川奉延、高橋孝雄

小児科 48 1095 - 1097 2007年

早発乳房

長谷川奉延

ホと臨床 55 251 - 253 2007年

KIGS Publications

大薗恵一、長谷川奉延

ホと臨床 55 801 - 809 2007年

副腎皮質ホルモン補充療法

鈴木亜由子、長谷川奉延

日本臨床 66 157 - 162 2007年

先天性副腎低形成症

天野直子、長谷川奉延

小児科 44 1677 - 1681 2007年

高インスリン血性低血糖症の診断と治療ガイドライン

長谷川奉延、田中敏章、神崎晋、杉原茂孝、横谷進、田中弘之、原田正平、藤枝憲二

日本小児科学会雑誌 110 1472 - 1474 2006年

Analyasis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

Visser R, HASEGAWA T, Niikawa N, Matsumoto N

J Hum Genet 51 15-20 2006年

研究論文（学術雑誌）, 共著, 査読有り

Growth-chart-based qualitative evaluation for height growth after hematopoietic stem cell transplantation.

Narumi S, Hasegawa T, Shimada H, Shimasaki N, Takahashi T, Mori T

Pediatric Transplantation 10 26 - 30 2006年

共著

Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: Diagnostic value of urine steroid hormone analysis.

Fukami M, Hasegawa T, Horikawa R, Ohashi T, Nishimura G, Homma K, Ogata T

Pediatr Res 59 276 - 280 2006年

共著

バニリルマンデル酸(VMH)、ホモバニリン酸(HVA) 　最新臨床検査のABC

長谷川奉延

日本医師会雑誌 135 （特別号(2) ） S250 2006年

単著

17-ヒドロキシプロジェステロン（17-OHP）最新臨床検査のABC

長谷川奉延

日本医師会雑誌 135 （特別号(2) ） S269 2006年

単著

ガラクトース、フルクトース最新臨床検査のABC

長谷川奉延

日本医師会雑誌 135 （特別号(2) ） S283 2006年

SF-1異常症

長谷川奉延

ホルモンと臨床 54 513 - 518 2006年

成長ホルモン分泌不全性低身長症

長谷川奉延

ドクターサロン 50 32 - 35 2006年

責任遺伝子の特定された副甲状腺機能低下症X連鎖劣性副甲状腺機能低下症

工藤京子、佐藤清二、長谷川奉延

ホと臨床 54 571 - 574 2006年

共著

成長障害（低身長）を伴う愛情遮断症候群

井ノ口美香子、長谷川奉延

日本臨床別冊内分泌症候群1 102 - 104 2006年

性腺形成不全

望月利美、長谷川奉延

日本臨床別冊内分泌症候群2 494 - 496 2006年

17α-ヒドロキシラーゼ欠損症

蜂屋瑠見、長谷川奉延

日本臨床別冊　内分泌症候群2 内分泌症候群2 689 - 691 2006年

11β-ヒドロキシラーゼ欠損症

鳴海覚志、長谷川奉延

日本臨床別冊内分泌症候群2 699 - 701 2006年

Russell-Silver症候群

小崎健次郎、泉幸佑、長谷川奉延

日本臨床別冊内分泌症候群3 436 - 439 2006年

性腺疾患（特集　内科疾患最新の治療―専門家からのアドバイス―）

鳴海覚志、長谷川奉延

内科 97 1404 - 1405 2006年

CRF負荷試験

吉田理恵、長谷川奉延

小児内科 38 1268 - 1269 2006年

ACTH負荷試験

天野直子、長谷川奉延

小児内科 38 1270 - 1272 2006年

内分泌疾患（特集：小児から成人へのキャリオーバー）

井ノ口美香子、長谷川奉延

小児科 47 1526 - 1532 2006年

外性器の異常

石井智弘、長谷川奉延

小児内科 38（増刊号　小児疾患の診断治療基準　第3版） 85 - 86 2006年

性分化の異常

石井智弘、長谷川奉延

小児内科 38（増刊号　小児疾患の診断治療基準　第3版） 218 - 220 2006年

成長期日本人における骨代謝動態の解析　若年発症神経性食欲不振症の骨密度

松崎健一郎、長谷川奉延、高石官成、戸山芳昭

Osteoporosis Japan 14 723 - 725 2006年

骨形成不全症の診療ガイドライン

田中弘之、田中敏章、神崎晋、杉原茂孝、横谷進、長谷川奉延、原田正平、藤枝憲二

日本小児科学会雑誌 110 1468 - 1471 2006年

古典的21-水酸化酵素欠損症

長谷川奉延

周産期医学 35 （ 12 ） 1645-1650 2005年12月

研究論文（学術雑誌）, 単著

包茎に対するステロイド薬塗布は効果があるのか？

堀　尚明,　長谷川奉延

小児内科 37 （ 11 ） 1559-1561 2005年11月

研究論文（学術雑誌）, 共著

T-box転写因子TBX3(TBX3)

佐々木悟郎,　長谷川奉延

生体の科学 56 （ 5 ） 370-371 2005年10月

研究論文（学術雑誌）, 共著

ヒトSF-1遺伝子異常症

長谷川奉延

日本生殖内分泌学会雑誌 10 55-57 2005年09月

研究論文（学術雑誌）, 単著

生殖補充医療と外陰部異常

長谷川奉延

ホルモンと臨床 53 701 - 706 2005年

単著

遺伝レベルよりみた性差

室谷浩二,　長谷川奉延

治療学 39 235-239 2005年

研究論文（学術雑誌）, 共著

Association of micropenis and pro185Ala polymorphism of the gene for aryl hydrocarbon receptor repressor involved in dioxin signaling.

Soneda S, Fukami M, Fujimoto M, Hasegawa T, Koitabashi Y, Ogata T.

Endocrine J 52 83-88 2005年

研究論文（学術雑誌）, 共著, 査読有り

Resumption of menstration and nutritional status in female patients with early onset anorexia nervosa.

Hori N, Inokuchi M, Yoshida R, Sato A, Choe M-S, Watanabe H, Hasegawa T.

Clin Pediatr Endocrinol 14 （ Suppl 22 ） 73-76 2005年

研究論文（学術雑誌）, 共著, 査読有り

Correlation between Insurin-like Growth Factor-Ⅰand Obesity Index during Inpatient Treatment in Anorexia Nervosa in Childhood and Adolescence

Myong-soon Choe, Sato A, Watanabe H,Hasegawa T

Clin Pediatr Endocrinol 14 （ Suppl 24 ） 21-23 2005年

研究論文（学術雑誌）, 共著, 査読有り

体質性思春期遅発症の治療は行うべきか？

七尾謙治、長谷川奉延

小児内科 37 1075 - 1077 2005年

共著

Two Novel and One Recurrent PTPN11 Mutations in LEOPARD Syndrome.

Yoshida R, Nagai T, Hasegawa T, Kinoshita E, Tanaka T, Ogata T.

Am J Med Genet 130A （ 4 ） 432-434. 2004年11月

研究論文（学術雑誌）, 共著, 査読有り

Premature ovarian failure in a female with proximal symphalangism and NOG mutation.

Kosaki K, Sato S, Hasegawa T, Matsuo N, Suzuki T, Ogata T.

Fertil Steril 81 （ 4 ） 1137-1139 2004年04月

研究論文（学術雑誌）, 共著, 査読有り

Genetic testing of glycogen storage disease type Ib in Japan: mutation spectrum in the G6PT1 gene and a rapid detection method for a prevalent W118R mutation.

Kojima K, Kure S, Kamada F, Hao K, Ichinohe A, Aoki Y, Suzuki Y, Kubota M, Horikawa R, Utsumi A, Miura M, Ogawa S, Kanazawa M, Inokuchi M, Hasegawa T, Narisawa K, Matsubara Y.

Mol Genet Metab 81 （ 4 ） 343-346 2004年04月

研究論文（学術雑誌）, 共著, 査読有り

Clinical assessment and mutaion analysis of Kallmann syndrome a (KAL1) and fibroblast growth factor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.

Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, HasegawaY, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T.

J Clin Endocrinol Metab 89 （ 3 ） 1079-1088 2004年03月

研究論文（学術雑誌）, 単著, 査読有り

GATA3ハプロ不全の多彩な臨床像 11家系20症例の検討

室谷浩二、長谷川奉延、長谷川行洋、坪内肯二、中込美子、菊池信行、伊藤善也、藤田敬之助、深見真紀、緒方勤

ホルモンと臨床 52 965 - 970 2004年

単著

Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mitation of steroidogenic factor-1

HASEGAWA TOMONOBU

J Clin Endocrinol Metab 89 （ 12 ） 5930-5935 2004年

研究論文（学術雑誌）, 共著, 査読有り

Two novel and recurrent PTPN11 mutations in LEOPARD syndrome

長谷川奉延

Am J Med Genet 130A （ 4 ） 432-434 2004年

研究論文（学術雑誌）, 共著, 査読有り

Multiple polypoid masses in gastrointestinal tract in Menkes disease during copper-histidine therapy

Sasaki G, Ishii T, Sato S, Hoshino K, Morikawa Y, Kodama H, Matsuo N, Takahashi T, Hasegawa T

Eur J Pediatr 163 （ 12 ） 745-746 2004年

研究論文（学術雑誌）, 共著, 査読有り

Protein-tyrosine phosphotase, nonreceptor type 11 mutation and clinical assessment in 45 patients with Noonan syndrome

Yoshida R, Hasegawa T, Hasegawa Y, Nagai T, Kinoshita E, Tanaka Y, Kanegane H, Ohyama K, Onishi T, Hanew K, Okuyama T, Hoikawa R, Tanaka T, Ogata T.

J Clin Endocrinol Metab 89 （ 7 ） 3359-3364 2004年

研究論文（学術雑誌）, 共著, 査読有り

Testosterone enanthate therapy is effective and independent of SRD5A2 and AR gene polymorphisms in 53 Japanese boys with micropenis

Ishii T, Sasaki G, Hasegawa T, Sato S, Matsuo N, Ogata T

J Urol 172 （ 1 ） 319-323 2004年

研究論文（学術雑誌）, 共著, 査読有り

Hyperinsulinemic hypoglycemia in a newborn infant with trisomy 13

Tamame T, Hori N, Homma H, Yoshida R, Inokuchi M, Kosaki K, Takahashi T, Hasegawa T.

Am J Med Genet 129A （ 3 ） 321-322 2004年

研究論文（学術雑誌）, 共著, 査読有り

A newly recognized syndrome of metaphyseal undermodeling, spondylar dysplasia and overgrowth: report of three sporadic patients

Nishimura G, Hasegawa T, Kinoshita E, Tanaka Y, Kurosawa K, Yoshimoto M.

Am J Med Genet 128A （ 2 ） 204-208 2004年

研究論文（学術雑誌）, 共著, 査読有り

A new diagnostic test for very-long-chain acyl-CoA dehydrogenase deficiency using immunohistochemistry

Ohashi Y, Hasegawa Y, Murayama K, Ogawa M, Hasegawa T, Kawai M, Sakata N, Yoshida K, Kamata H, Imai K, Kumagai I, Murakami K, Hasegawa H, Noguchi S, Nonaka I, Yamaguchi S, Nishino I.

Neurology 62 （ 12 ） 2209-2213 2004年

研究論文（学術雑誌）, 共著, 査読有り

Metaphyseal dysplasia Jansen type　骨幹端異形成症Jansen型

佐々木悟郎,　長谷川奉延

小児内科 36 （増刊） 374−375 2004年

研究論文（学術雑誌）, 共著

Type II microcephalic osteodysplastic dysplasia　小頭性骨異形成異形成症II型

堀尚明, 長谷川奉延

小児内科 36 （増刊） 199−201 2004年

研究論文（学術雑誌）, 共著

Low birth weight slender bone group　低出生体重の細長い骨疾患グループ—概説

堀尚明, 長谷川奉延

小児内科 36 （増刊） 197−198 2004年

研究論文（学術雑誌）, 共著

先天性リポイド副腎過形成症の乳児の卵巣機能

上牧務, 長谷川奉延

ホルモンと臨床特集内分泌興味ある症例　第45集 52 （増刊） 104−107 2004年

研究論文（学術雑誌）, 共著

学校における神経性食欲不振症早期発見の試み

田中徹哉, 石井敬子, 廣金和枝, 佐藤明弘, 崔明順, 藤田尚代, 長谷川奉延, 徳村光昭, 川合志緒子, 南里清一郎, 木村慶子, 渡辺久子

慶應保健研究 22 55-59 2004年

研究論文（学術雑誌）, 共著

Noonan症候群の遺伝的基盤

吉田理恵, 谷川奉延, 緒方勤

小児科診療 67 1599-1604 2004年

研究論文（学術雑誌）, 共著

自己免疫性多腺性症候群

石井智弘, 長谷川奉延, 鈴木賀巳

小児内科 36 1550-1553 2004年

研究論文（学術雑誌）, 共著

Enchondromaatosis (Ollier) 内軟骨腫症 (Ollier病)

佐々木悟郎, 長谷川奉延

小児内科 36 （増刊） 257−259 2004年

研究論文（学術雑誌）, 共著

Type II microcephalic osteodysplastic dysplasia　小頭性骨異形成異形成症II型

堀尚明, 長谷川奉延

小児内科 36 （増刊） 199−201 2004年

研究論文（学術雑誌）, 共著

Low birth weight slender bone group　低出生体重の細長い骨疾患グループ—概説

堀尚明, 長谷川奉延

小児内科 36 （増刊） 197−198 2004年

研究論文（学術雑誌）, 共著

先天性リポイド副腎過形成症の乳児の卵巣機能

上牧務, 長谷川奉延

ホルモンと臨床　特集内分泌興味ある症例　第45集 52 （増刊） 104−107 2004年

研究論文（学術雑誌）, 共著

外性器異常を有し生後3週まで社会的性を決定されなかった1例

鈴木亜由子, 井ノ口美香子, 下郷幸子, 佐々木理恵, 堀尚明, 長谷川奉延, 高橋孝雄

小児科臨床 57 113-119 2004年

研究論文（学術雑誌）, 共著

Genomic organization and sequence variation of the human integrin subunit 8 gene (ITGA8).

Ekwa-Ekoba C, Diaz G, Carlson C, Hasegawa T, Lim K-c, Yabu J, Levy B, Schnapp LM.

Matrix Biol 23 487-496 2004年

研究論文（学術雑誌）, 共著, 査読有り

Elevated urine pregnanetriolone definitively establishes the diagnosis of classical 21-hydroxylase deficiency in term and preterm neonates.

Homma K, Hasegawa T, Takeshita E, Watanabe K, Anzo M, Toyoura T, Jinno K, Ohashi T, Hamajima T, Takahashi Y, Takahashi T, Matsuo N.

J Clin Endocrinol Metab 89 6087-6091 2004年

研究論文（学術雑誌）, 共著, 査読有り

A case of preterm infant with 21-hydroxylase deficiency; the implication of the biochemical diagnosis by urinary pregnanetriolone using GCMS-SIM (gas chromatography mass spectrometry-selected ion monitoring).

Hamajima T, Ohki S, Mizuno H, Homma K, Hasegawa T.

Clin Pediatr Endocrinol 13 65-70 2004年

研究論文（学術雑誌）, 共著, 査読有り

Transient hyper17-OHPnemia unremated to cross-reactions with residual fetal adrenal cortex products.

Mizuno H, Ohro Y, Sugiyama Y, Ito T, Hasegawa T, Homma K, Ueshiba H, Togari H.

Hor Res 61 （ 5 ） 242-245 2004年

研究論文（学術雑誌）, 共著, 査読有り

Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1.

Hasegawa T, Fukami M, Sato N, Katsumata N, Sasaki G, Fukutani K, Morohashi K-i, Ogata T

J Clin Endocrinol Metab 89 5930 - 1935 2004年

共著

Reference values for urinary steroids in Japanese newborn infants: gas chromatography/mass spectrometry in selected ion monitoring.

Homma K, Hasegawa T, Masumoto M, Takeshita E, Watanabe K, Chiba H, Kurosawa T, Takahashi T, Matsuo N.

Endocrine J 50 （ 6 ） 783-792 2003年12月

研究論文（学術雑誌）, 単著, 査読有り

Longitudinal auxological study in female with SHOX haploinsufficiency and normal ovarian function.

Fukami M, Matsuo N, Hasegawa T, Sato S, Ogata T.

Eur J Endocrinol 149 （ 4 ） 337-341 2003年10月

研究論文（学術雑誌）, 共著, 査読有り

Micropenis and the 5-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients.

Sasaki G, Ogata T, Ishii T, Kosaki K, Sato S, Homma K, Takahashi T, Hasegawa T, Matsuo N.

J Clin Endocrinol Metab 88 （ 7 ） 3431-3436 2003年07月

研究論文（学術雑誌）, 共著

Mental retardation in a boy with congenital adrenal hypoplasia: a clue to contiguous gene syndrome involving DAX1 and IL1RAPL

Sasaki Rie, Inamo Yasugi, Saitoh Kazumasa, Hasegawa Tomonobu, Kinoshita Eiichi, Ogata Tsutomu

Endocrine journal 50 （ 3 ） 303-307 2003年06月

研究論文（学術雑誌）, 共著, 査読有り

Giant seminoma in a patient with 5a-reductase-2 deficiency

Sasaki Gen, Nakagawa Ken, Hashiguchi Akinori, Hasegawa Tomonobu, Ogata Tsutomu, Murai Masaru

Journal of urology 169 （ 3 ） 1080-1081 2003年03月

研究論文（学術雑誌）, 共著

Micropenis and the 5a-reductase-2 (SRD5A2) gene: mutation and V89L polymorphism analysis in 81 Japanese patients

Sasaki Goro, Ogata Tsutomu, Ishii Tomohiro, Kosaki Kenjiro, Sato Seiji, Homma Keiko, Takahashi Takao, Hasegawa Tomonobu, Matsuo Nobutake

Journal of clinical endocrinology and metabolism 88 （ 7 ） 3431-3436 2003年

研究論文（学術雑誌）, 共著

Giant seminoma in a patient with 5 alpha-reductase type 2 deficiency

Sasaki Goro, Nakagawa Ken, Hashiguchi Akinori, Hasegawa Tomonobu, Ogata Tsutomu, Murai Masaru

Journal of urology 169 1080-1081 2003年

研究論文（学術雑誌）, 共著

Microcephalic osteodysplastic primordial dwarfism type II with Cafe-au lait spots and Moyamoya disease

Nishimura Gen, Hasegawa Tomonobu, Hori Naoaki, Fujino Motoko, Tomita Yukiharu.

American journal medical genet 117A 299-301 2003年

研究論文（学術雑誌）, 共著

Final height of female patients with early-onset anorexia nervosa

Hori Naoaki, Inokuchi Mikako, Sasaki Rie, Myong-sun, Watanabe Hisako, Hasegawa Tomonobu

Clinical Pediatric Endocrinology 87 （ 8 ） 2003年

研究論文（学術雑誌）, 共著

Final height of female patients with early-onset anorexia nervosa.

Hori N, Inokuchi M, Sasaki R, Choe M-s, Watanabe H, Hasegawa T.

Clin Pediatr Endocrinol 12 （ Supple20 ） 77-79 2003年

研究論文（学術雑誌）, 共著, 査読有り

Ischiospinal dysostosis with cystic kidney disease: report of two cases

Nishimura G, Kim OH, Satoh S, Hasegawa T.

Clin Dysmorphol 12 101-104 2003年

研究論文（学術雑誌）, 共著, 査読有り

生後2ヶ月まで17OHP高値が遅延し，診断に苦慮したマススクリーニング陽性者の一例

水野晴夫，杉山由賀里，伊藤哲哉，戸苅創，大呂陽一郎，長谷川奉延，本間桂子，上芝元

ホルモンと臨床 50冬季増刊号（ 12 ） 118-120 2002年12月

研究論文（学術雑誌）, 共著

Lack of correlation between the endocrinological abnormalities and obesity index in anorexia nervosa in childhood and adolescence.

Inokuchi M, Hasegawa T, Hori N, Choe M-s, Tokita N, Watanabe H, Matsuo N.

Clin Pediatr Endocrinol 11 （ Suppl17 ） 73-75 2002年11月

研究論文（学術雑誌）, 共著, 査読有り

ACTH不応症

佐々木悟郎，石井智弘，長谷川奉延

小児内科 34 （増刊） 676-679 2002年11月

研究論文（学術雑誌）, 共著

The roles of circulating high density lipoproteins and trophic hormones in the phenotype of knockout mice lacking the steroidogenic acute regulatory protein.

Hasegawa T, Ishii T, Pai C-I, Yvgi-Ohana N, Timberg R, Zhao L, Majdic G, Chung B-c, Orly JC, Parker KL.

Mol Endocrinol 16 （ 10 ） 2297-2309 2002年10月

研究論文（学術雑誌）, 共著, 査読有り

Autopsy case of microcephalic osteodysplastic primordial 'dwarfism' type II

Fukuzawa Ryuji, Sato Seiji, Sullivan Michael J, Nishimura Gen, Hasegawa Tomonobu, Matsuo Nobutake

Am J Med Genet 113 （ 1 ） 93-96 2002年08月

研究論文（学術雑誌）, 共著

GH / IGFIと男性性腺機能

佐々木悟郎，長谷川奉延

内分泌糖尿病科15 15 （ Suppl1 ） 157-160 2002年08月

研究論文（学術雑誌）, 共著

Duplication of 8p23.2: a benign cytogenetic variant ?

Harada Naoki, Takano Jun, Kondoh Tatsuro, Ohashi Hirofumi, Hasegawa Tomonobu, Sugawara Hirobumi, Ida Tomoko, Yoshiura Koichiro, Ohta Tohru, Kishino Tatsuo, Kajii Tadashi, Niikawa Norio, Matsumoto Naomichi

Am journal of medical genetics 111 （ 3 ） 285-288 2002年08月

研究論文（学術雑誌）, 共著

性腺機能低下症

井ノ口香子，長谷川奉延

小児科診療 65 （増刊） 403-404 2002年04月

研究論文（学術雑誌）, 共著

Characterization of the aryl hydrocarbon receptor repressor gene and association of its Pro185Ala polymorphism with micropenis

Fujita H, Kosaki R, Yoshihashi H, Ogata T, Tomita M, Hasegawa T, Takahashi T, Matsuo N, Kosaki K

Teratology 65 （ 1 ） 10-18 2002年01月

研究論文（学術雑誌）, 共著

ミクロペニス

佐々木悟郎、長谷川奉延

小児科診療) 65 1579 - 1583 2002年

共著

IGF-1による治療　(1) 成長ホルモン (GH) 不応症

松尾宣武，長谷川奉延

成長発達（ 9 ） 4-6 2002年

研究論文（学術雑誌）, 共著

成長ホルモン適応基準の解説

上牧務，長谷川奉延

小児科臨床（ 55 ） 1243-1250 2002年

研究論文（学術雑誌）, 共著

生後2ヶ月まで17-OHP高値が遷延し，診断に苦慮したマススクリーニング陽性者の1例

水野晴夫，杉山由賀里，伊藤哲哉，戸苅創，大呂陽一郎，長谷川奉延，本間桂子，上芝元

ホルモンと臨床 50 （増刊号） 118-120 2002年

研究論文（学術雑誌）, 共著

Novel mutation of TBX3 in a Japanese family with ulnar-mammary syndrome

Sasaki Goro, Ogata Tsutomu, Ishii Tomohiro, Hasegawa Tomonobu, Sato Seiji, Matsuo Nobutake

Am J Med Genet 110 （ 4 ） 365-369 2002年

研究論文（学術雑誌）, 共著

Lack of correlation between the endocrinological abnormalities and obesity index in anorexia nervosa in childhood and adolescence

Inokuchi Mikako, Hasegawa Tomonobu, Hori Naoaki, Choe Myong-sun, Tokita Natsuko, Watanabe Hisako, Matsuo Nobutake

Clinical Pediatric Endocrinology 11 （ Suppl17 ） 73-75 2002年

研究論文（学術雑誌）, 共著

A case of impairment of mitochondrial fatty acid β-oxidation (Clinico-pathological conference).

Hasegawa T, Hori N, Du W.

Keio J Med 51 100 - 106 2002年

共著

SF-1遺伝子異常症、WT1異常症

長谷川奉延

小児科診療 65 1564 - 1569 2002年

単著

出生後に甲状腺機能亢進症を呈した,胎内治療を行った甲状腺腫性甲状腺機能低下症の1例

佐藤清二，井ノ口美香子，佐々木悟郎，北東功，石井智弘，長谷川奉延，池田一成，松尾宣武

ホルモンと臨床 49 （ 12 ） 1159-1162 2001年12月

研究論文（学術雑誌）, 共著

Female gonadal development in XX patients with distal 9p monosomy

Ogata T, Muroya K, Ohashi H, Mochizuki H, Hasegawa T, Kaji M

European Journal of Endocrinology 145 （ 5 ） 613-617 2001年11月

研究論文（学術雑誌）, 共著

GATA3 abnormalities and the phenotypic spectrum of HDR syndrome

Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, Yamamoto K, Fujimoto S, Seishu S, Fukushima Y, Hasegawa Y, Ogata T

Journal Medical Genetics 38 （ 6 ） 374-380 2001年06月

研究論文（学術雑誌）, 共著

Melnick-Needles症候群

長谷川奉延

小児科診療 64 （ 3 ） 406 2001年03月

研究論文（学術雑誌）, 単著

性染色体異常症候群

長谷川奉延

臨床検査 45 （ 2 ） 143-150 2001年02月

研究論文（学術雑誌）, 単著

女子性腺機能低下症

長谷川奉延

ホルモンと臨床　増刊号「臨床に役立つ内分泌疾患診療マニュアル2001」 49 （増刊号） 165-168 2001年01月

研究論文（学術雑誌）, 単著

EEC症候群

長谷川奉延

小児科診療 64 （ 1 ） 30 2001年01月

研究論文（学術雑誌）, 単著

出生後に甲状腺機能亢進症を呈した,胎内治療を行った甲状腺腫性胎児甲状腺機能低下症の1例

佐藤清二，井ノ口美香子，佐々木悟郎，北東功，石井智弘，長谷川奉延，池田一成，松尾宣武

日本小児科学会雑誌 105 599 2001年

研究論文（学術雑誌）, 共著

【小児内分泌疾患の診断基準・治療のガイドラインUPDATE】　性腺　新生児半陰陽

長谷川奉延

ホルモンと臨床 49 967-974 2001年

研究論文（学術雑誌）, 単著

【副腎疾患の診断基準・治療のガイドラインUPDATE】　副腎皮質疾患〈機能亢進症〉　21水酸化酵素欠損症

長谷川奉延

ホルモンと臨床 49 579-585 2001年

研究論文（学術雑誌）, 単著

SF-1遺伝子異常症

長谷川奉延

小児科診療 64 932-933 2001年

研究論文（学術雑誌）, 単著

【染色体　検査と社会とのかかわり】　性染色体異常症候群

長谷川奉延

臨床検査 45 143-150 2001年

研究論文（学術雑誌）, 単著

小児の症候群　骨・関節・結合職　Melnick-Needles症候群

長谷川奉延

小児科診療 64 408 2001年

研究論文（学術雑誌）, 単著

【小児の症候群】　染色体・奇形　EEC症候群

長谷川奉延

小児科診療 64 30 2001年

研究論文（学術雑誌）, 単著

【臨床に役立つ内分泌疾患診療マニュアル2001】　女子性腺機能低下症　(1)原発性性腺機能低下症　(2)続発性性腺機能低下症

長谷川奉延

ホルモンと臨床 49 165-168 2001年

研究論文（学術雑誌）, 単著

Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata

Ikegawa S, Ohashi H, Ogata Tsutomu, Honda A, Tsukahara M, Kubo T, Kimizuka M, Shimode M, Hasegawa Tomonobu, Nishimura G, Nakamura Y

American Journal of Human Genetics 94 （ 4 ） 300-305 2000年10月

研究論文（学術雑誌）, 共著

SF-1遺伝子異常症

長谷川奉延

ホルモンと臨床 48 （ 8 ） 715-722 2000年08月

研究論文（学術雑誌）, 単著

Digynic triploid infant surviving for 46days

Hasegawa Tomonobu, Harada N, Ikeda Kazushige, Ishii Tomohiro, Hokuto Isamu, Kasai Kenji, Tanaka Mamoru, Fukuzawa Ryuji, Niikawa N, Matsuo Nobutake

American journal of medical genetics 87 （ 4 ） 306-310 1999年12月

研究論文（学術雑誌）, 共著

Spondylo-metaphyseal dyaplasia with regressive platyspondyly

Hasegawa T, Kozloowski K, Nishimura G, Hara H, Hasegawa Y, Aso T, Kato S, Nagai T, Tsuchiya Y

Locomotor System 6 （ 1 ） 53-59 1999年11月

研究論文（学術雑誌）, 共著

薬剤の臨床小児便秘症に対するML-P(ラクツロース散剤）の有用性の検討

辻敦敏，松尾宣武，長谷川奉延，白幡聡，梶原康巨，郡建男，石塚丈広，森泰二郎，竹田周吾，萩原誠一，長谷川元宏

小児科診療 61 （ 3 ） 451 1998年

研究論文（学術雑誌）, 共著

Free from insulin－like growth factor-1 in circulation is normal in children with simple obesity

Hasegawa Tomonobu, Takada Yukihiro, Takada Makoto, Ishii Tomohiro, Sato Seiji, Matsuo Nobutakae

Hormone Research 49 （ Suppl 1 ） 51 1998年

研究論文（学術雑誌）, 共著

Joint laxity, vitreoretinal degeneration, facial abnormalities, and generalized skeletal alterations:A new syndrome?

Nishimura Gen, Hasegawa Tomonobu, Sugii Kyoko, Tsuyama Kaiichiro, Matsuo Nobutake

Journal of Human Genetics 43 （ 3 ） 191-194 1998年

研究論文（学術雑誌）, 共著, 査読有り

A case of de novo interstitial deletion of chromosome 7, del(7)(q31,2q32)

Hasegawa Tomonobu, Nagai Toshiro, Yamada Ken-ichiro, Tsuchiya Yutaka

Acta Med Auxol 29 （ 3 ） 165-169 1997年12月

研究論文（学術雑誌）, 共著

真性半陰陽を有する SRY negative XX maleの一例：内性器の検討と成因の考察

永井敏郎，川目裕，黒澤健司，木下英一，緒方勤，長谷川奉延，松尾宣武，中井秀郎

ホルモンと臨床 45 （臨時増刊） 225-228 1997年11月

研究論文（学術雑誌）, 共著

尿中アルドステロン，18-ヒドロキシコルチコステロンおよび18-ヒドロキシコルチゾール代謝物の基準値および臨床応用

本間桂子，竹下栄子，渡辺清明，上牧務，長谷川奉延，佐藤清二，猿田享男，村井勝，松尾宣武

ホルモンと臨 45 （ 9 ） 813-821 1997年09月

研究論文（学術雑誌）, 共著

性腺形成不全と染色体

長谷川奉延，松尾宣武

産と婦 64 （ 5 ） 613-617 1997年05月

研究論文（学術雑誌）, 共著

Pit-1異常症（先天性GH,PRL,TSH複合欠損症）

長谷川奉延

小児科 38 （ 3 ） 235-235 1997年03月

研究論文（学術雑誌）, 単著

先天性TSH単独欠損症

長谷川奉延

小児科 38 （ 2 ） 108-108 1997年02月

研究論文（学術雑誌）, 単著

Further clnical model for the possible impairment of a putative lymphogenic gene(s) for Turner stigmata

Ogata Tsutomu, Hasegawa Tomonobu, Matsuo Nobutake

Hum Genet 99 （ 2 ） 290-290 1997年02月

研究論文（学術雑誌）, 共著

High ration of free to total insulin-like growth factor- I in early infancy

Hasegawa Yukihiro, Hasegawa Tomonobu, Fujii Katsura, Koni Hideko, Anzo Makoto, Aso Taiji, Koto Shinobu, Takada Makoto, Tsuchiya Yutaka

J Clin Endocrinol Metab 82 （ 1 ） 156-158 1997年01月

研究論文（学術雑誌）, 共著

Serum acid-labile subunit is a good parameter for diagnosis of GH deficiency

Yamada Makoto, Fujii Katsura, Hasegawa Tomonobu, Hasegawa Yukihiro

Clin Pediatr Endocrinol 6 （ Suppl 9 ） 99-101 1997年

研究論文（学術雑誌）, 共著

A case of skeletal dysplasia with advanced carpal ossification and 'monkey wrench' appearance of the femora:mild Desbuquois dysplasia?

Nishimura Gen, Sato Seiji, Ogata Tsutomu, Tamai Shinya, Hasegawa Tomonobu, Matsuo Nobutake

Eur J Pediatr 155 1040-1042 1996年12月

研究論文（学術雑誌）, 共著

周期的月経を有するTurner症候群の1例

田中紀子，長谷川行洋，長谷川奉延，土屋裕

小児科診療 59 （ 9 ） 1515-1518 1996年09月

研究論文（学術雑誌）, 共著

小児内分泌科医の提案するGender Assignmentの原則

長谷川行洋，長谷川奉延

泌尿器外科 9 （ 7 ） 563-568 1996年07月

研究論文（学術雑誌）, 共著

Short term growth hormone treatment for a girl with osteodysplastic primordial dwarfism type II

Sato Seiji, Anzo Makoto, Hasegawa Tomonobu, Kamimaki Tsutomu, Matsuo Nobutake

Clin Pediatr Endocrinol 5 （ Suppl.8 ） 139-141 1996年06月

研究論文（学術雑誌）, 共著

Clinical utility of insulin-like growth factor-I (IGF-I)and IGFbinding protein-3 levels in the diagnosis of GH deficiency(GHD)during childhood

Hasegawa Yukihiro, Hasegawa Tomonobu, Anzo Makoto, Aso Taiji, Tsuchiya Yutaka

Endcr J 43 （ Suppl ） S1-S4 1996年05月

研究論文（学術雑誌）, 共著

Coarctation of the aorta and renal hypoplasia in a boy with Turner/Noonan surface anomalies and a 46,XY karyotype:a clinical model for the possible impairment of a putative lymphogenic gene(s) for Turner somatic stigmata

Hasegawa Tomonobu, Ogata Tsutomu, Hasegawa Yukihiro, Honda Masataka, Nagai Toshiro, Fukushima Yoshimitsu, Nakahori Yutaka, Matsuo Nobutake

Hum Genet 97 （ 5 ） 564-567 1996年05月

研究論文（学術雑誌）, 共著

ガスクロマトグラフ質量分析法による尿ステロイド分析

松尾宣武，佐藤清二，緒方勤，長谷川奉延，安蔵慎，上牧務，室谷浩二，本間桂子，竹下栄子，渡辺清明

小児診 59 （ Suppl. ） 264-272 1996年04月

研究論文（学術雑誌）, 共著

軟骨異栄養症 (軟骨無形成症) 59症例に対する遺伝子組み換え技術によるヒト成長ホルモン (NN-798) の成長促進効果の検討

清野佳紀、諏訪珹三、新美仁男、松尾宣武、安井夏生、鎮目和夫、日比逸郎、田中敏章、奥野晃正、藤枝憲二、五十嵐裕、佐藤清二、土屋裕、立花克彦、安田敏行、大山建司、五十嵐良雄、小川正道、衣笠昭彦、須藤正克、山岡完次、郷司克己、田中弘之、西美和、貴田嘉一、倉繁隆信、宮田晃一郎、小野星吾、西山宗六、河野斉、玉那覇栄一、伊藤善也、長谷川行洋、長谷川奉延、麻生泰二、南谷幹史、小川治夫、浅井寿、山本威久、久保俊英、伊藤卓夫、荒木久美子、大坪修介、宮里善次

ホルモンと臨床 43 77 - 86 1995年

共著

Clinical utility of total insulin-like growth factor-I and insulin-like growth factor binding protein-3 measurements in the evaluation of short children.

Hasegawa Y, Hasegawa T, Tsuchiya Y.

Clin Pediatr Endocrinol 4 103 - 113 1995年

共著

Clinical information on serum IGFBP-3 levels and IGFBP-3 proteolytic activity in childhood.

Hasegawa Y, Hasegawa T, Fujii K, Konii H, Anzo M, Aso T, Kotoh S, Tsuchiya Y

Prog Growth Factor Res 6 457 - 463 1995年

共著

友達の輪

長谷川奉延

さかえ 34 37 1994年

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